PMID: 24707167

Gene: VHL

StandardizedReferenceSequence: NM_000551.3

PatientID: 3

KindredID: 1

Case: M, 55Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: This patient was a member of family 1, where 14/32 total patients were diagnosed with VHL. One of which (I-32) was a mutational carrier with down syndrome. The other 13 patients had varying phenotypes, including adrenal pheochromocytoma, pancreatic endocrine tumors, liver and bone metastases, paraganglioma, cerebellar, spinal, and retinal hemangioblastomas, polycythemia, and chondrosarcoma. See Fig. 1 for family pedigree.

CasePresentingHPOs: HP:0006748; HP:0002668; HP:0030405; HP:0009713; HP:0006880; HP:0001901 (adrenal pheochromocytoma; paraganglioma; pancreatic endocrine tumor; spinal hemagnioblastoma, cerebellar hemagnioblastoma; polycythemia)

CaseHPOFreeText: Patient presented with his initial VHL-related clinical manifestations at 7Y0M. He was found to have adrenal pheochromocytoma; paraganglioma, pancreatic endocrine tumor, spinal and cerebellar hemagnioblastoma, and polycythemia (see table 1). Patient was diagnosed with VHL subtype 2A at 54Y0M.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 8550742

SupplementalData: N/A

Variant: p.V166F (c.496G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 2224, https://www.ncbi.nlm.nih.gov/clinvar/variation/2224/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: V166F (c.496G>T)

MultipleGeneVariants: N/A

PatientID: III-10

KindredID: 1

Case: F, 27Y0M, Turkish

DiseaseAssertion: VHL

FamilyInfo: 17 family members from three generations were examined with the c.445G>T mutation and diagnosed with VHL type 2B. 11 individuals had clinical manifestations and 6 were asymptomatic carriers. One additional member (II-9) had passed before testing however were likely a carrier of the mutation. This patient’s mother, brother, and more, had the mutation. See Fig. 1 for full family pedigree.

CasePresentingHPOs: HP:0006748; HP:0005584 (adrenal pheochromocytoma; renal cell carcinoma)

CaseHPOFreeText: bilateral adrenal pheochromocytoma, right RCC

CaseNotHPOs: HP:0030393; HP:0009715 (endolymphatic sac tumor, papillary cystadenoma of the epididymis) 

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.A149S (c.445G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 127829 https://www.ncbi.nlm.nih.gov/clinvar/variation/127829/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: A149S (c.445G>T)

MultipleGeneVariants: N/A

GroupID/ KindredID: F54

Case: Sex unknown, 31Y0M, Spanish

DiseaseAssertion: assumed VHL

FamilyInfo: None.

CasePresentingHPOs: HP:0006880; HP:0000107; HP:0001737 (cerebellar hemangioblastoma, renal cysts, pancreatic cysts)

CaseHPOFreeText: Age of onset is 31Y0M.

CaseNotHPOs: HP:0006770; HP:0002666; HP:0009711 (clear cell renal cell carcinoma, pheochromocytoma, retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.F76del (c.227_229del)

LegacyVariant: g.941_943delTCT

CaseProblemVariantFreeText: Patient was reported with the g. (genomic) coding positions. The g.941_943delTCT variant worked out to correspond with c.227_229delTCT.

ClinVarID: N/A

CAID: CA357012 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.227_229del

gnomAD: N/A

VariantEvidence: N/A

MutationType: inframe_deletion

CivicName: F76del (c.227_229del)

MultipleGeneVariants: N/A

PatientID: II:3 (proband 4)

KindredID: 4

Case: M, 38Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: Patient’s mother (I:1) was found with the same mutation and RCC at 63Y. The proband’s brother (II:1) died before diagnosis; thus no DNA sample available. He presented with hemangioblastoma at 19Y

CasePresentingHPOs: HP:0010797; HP:0009711 (hemangioblastoma, retinal capillary hemangioma)

CaseHPOFreeText: patient had hemangioblastoma at 22Y and retinal capillary hemangioma at 32Y

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.N90I (c.269A>T)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 223172 https://www.ncbi.nlm.nih.gov/clinvar/variation/223172/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: N90I (c.269A>T)

MultipleGeneVariants: N/A

GroupID: 22

DiseaseAssertion: assumed VHL

GroupSize: 3

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: 3 of the 573 patients discussed in this paper were found to have the following mutation belonging to 1 family. 

GroupPresentingHPOs: HP:0006880; HP:0009711; HP:0005584 (cerebellar hemangioblastoma, retinal capillary hemangioma; renal cell carcinoma)

GroupHPOFreeText: 1 patient had retinal angiomas diagnosed at the age of 15Y, 1 had cerebellar hemangioblastomas diagnosed at 20Y, and 1 member had RCC diagnosed at 38Y.

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

Variant: p.H125Qfs*7 (c.374dupA)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA2499307153 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2499307153

gnomAD: N/A

VariantEvidence: N/A

MutationType: duplication

CivicName: H125fs (c.374insA) 

MultipleGeneVariants: N/A

PMID: 28721348

Gene: VHL

StandardizedReferenceSequence: NM_000551.3

PatientID: None

KindredID: 4

Case: M, 34Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: None.

CasePresentingHPOs: HP:0010797, HP:0005584 (hemangioblastoma, renal cell carcinoma)

CaseHPOFreeText: The patient had three tumours, one hemangioblastoma of the central nervous system and two renal cell carcinomas.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: Previously published in 24301059.

SupplementalData: N/A

Variant: p.Q164* (c.490C>T)

LegacyVariant: N/A

ClinVarID: 223228 https://www.ncbi.nlm.nih.gov/clinvar/variation/223228/

CAID: N/A

gnomAD: N/A

VariantEvidence: The patient had a mosaic mutation with a mutated allele frequency of 3.3%. Copy number events of the mutated and wild type allele are available in table S4 of the supplemental.

MutationType: stop_gained

CivicName: Q164* (c.490C>T)

MultipleGeneVariants: N/A

PatientID: N/A

KindredID: 20

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Family history not mentioned. Patient’s variant reported as germline.

CasePresentingHPOs: HP:0010797; HP:0005584 (Hemangioblastoma, Renal cell carcinoma)

CaseHPOFreeText: Patient had VHL disease type 1; CNS-HB and RCC (see table 1).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 2624160

SupplementalData:  N/A

Variant: p.F76del (c.227_229del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA357012, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.227_229delTCT

gnomAD: N/A

VariantEvidence: Variant reported as c.226_228del and was mapped to c.227_229del.

MutationType: inframe_deletion

CivicName: F76del (c.227_229del)

MultipleGeneVariants: N/A

PatientID: 4

KindredID: 3

Case: M, 45Y0M, Arab

DiseaseAssertion: VHL

FamilyInfo: No family history of VHL disease was described for this patient. Immediate family members were recommended to genetically test for the relevant variant or monitor for VHL-related symptoms.

CasePresentingHPOs: HP:0006880; HP:0009713; HP:0000107; HP:0001737; HP:0000787 (cerebellar hemangioblastoma; spinal hemangioblastoma; renal cyst; pancreatic cysts; nephrolithiasis)

CaseHPOFreeText: At 40Y, Patient 4 was diagnosed with spinal and cerebellar hemangioblastomas, as well as multiple renal and pancreatic cysts. He was diagnosed with VHL disease type 1. At 43Y, renal cysts and stones were discovered. A year later, more spinal hemangioblastomas and renal stones were found. A year later, cerebellar lesions, as well as renal and pancreatic cysts were reported (see table 1).

CaseNotHPOs: HP:0002088; HP:0001392; HP:0005264; HP:0001743 (abnormal lung morphology; abnormality of the liver; abnormality of the gallbladder; abnormality of the spleen)

CaseNotHPOFreeText: No lesions were observed in the lungs, liver, gallbladder, and spleen.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData:  N/A

Variant: p.N90del (c.268_270del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA645524783, https://reg.genome.network/redmine/projects/registry/genboree_registry/by_caid?caid=CA645524783

gnomAD: N/A

VariantEvidence: N/A

MutationType: inframe_deletion

CivicName: N90del (c.268_270del)

MultipleGeneVariants: N/A

PatientID: 378

KindredID: 378

Case: Sex Unknown, 52Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Family history is positive but no details are provided.

CasePresentingHPOs: HP:0010797 (Hemangioblastoma)

CaseHPOFreeText: CNS hemangioblastoma.

CaseNotHPOs: HP:0002666; HP:0006770; HP:0001732; HP:0000107; HP:0009711 (Pheochromocytoma, Clear cell renal cell carcinoma, Abnormality of the pancreas, Renal cyst, Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished:N/A

SupplementalData: Table S1, S2 and S3

Variant: Exon 1-2 Deletion (c.1-?_463+?del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: exon_loss_variant; deletion

CivicName: Exon 1-2 Deletion

MultipleGeneVariants: N/A

PMID: 7977367

Gene: VHL

StandardizedReferenceSequence: NM_000551.3

GroupID: 7

Case: Age unknown, Sex unknown, French

DiseaseAssertion: VHL

FamilyInfo: None - one member documented here

CasePresentingHPOs: N/A

CaseHPOFreeText: other manifestations are not clearly stated.

CaseNotHPOs: HP:0009711 (retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: Possibly published in PMID:15300849

SupplementalData: N/A

Variant: p.P71Lfs*61 (c.211_212insT)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA2501268513 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2501268513

gnomAD: N/A

VariantEvidence: N/A

MutationType: plus_1_frameshift

CivicName: P71fs (c.211insT)

MultipleGeneVariants: N/A

GroupID: 47

DiseaseAssertion: VHL

GroupSize: 15

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: French

GroupAgeRange: N/A

GroupInfo: 15 patients are listed with this mutationt; any relation is unknown.

GroupPresentingHPOs: HP:0009711 (retinal capillary hemangioma)

GroupHPOFreeText: 5 patients were said to have retinal HBs. Other manifestations are not clearly stated.

GroupNotHPOs: N/A

GroupNotHPOFreeText: the other 10 members are said to not have retinal HBs

GroupPreviousTesting: N/A

PreviouslyPublished: some are possibly published in PMID:15300849

SupplementalData: N/A

Variant: p.R167W (c.499C>T)

CaseProblemVariantFreeText: N.A

LegacyVariant: N/A

ClinVarID: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

CAID: N/A

gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: R167W (c.499C>T)

MultipleGeneVariants: N/A

PMID: 25557216

Gene: VHL

StandardizedReferenceSequence: NM_000551.3

PMID: 23632291

Gene: VHL

StandardizedReferenceSequence: NM_000551.3

ArticleReferenceSequence: Not specified – Assumption: variants assumed to have been documented by the author under reference sequence NM_000551.3

GenotypingMethod: Genomic DNA (50–100 ng) was amplified by polymerase chain reaction (PCR) in a standard PCR buffer containing 200 mM of each deoxyribonucleotide triphosphate (dNTP), 1.5 mM MgCl2, 0.25 units of Ex Taq™ DNA polymerase (TaKaRa, Dalian, China) and 0.2 mM of each primer. Any partial or complete VHL gene deletions were detected by real-time quantitative PCR (RQ-PCR).

SamplingMethod: peripheral blood leukocytes

PatientID: V-7

KindredID: 1

Case: F, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Family’s roots were traced to the German town of Leipzig in Saxony, from whence the original 11 siblings had immigrated to America around 1670. The following report is a 2011 updated pedigree on the previously reported Tisherman kindred. At the time of this study, 43/49 patients have undergone mutational analysis revealing the VHL familial mutation (Y112H) and 35/49 patients have clinical VHL manifestations. Phenotypic cumulative lifetime risk was 71% for Pheo/PGL, 15% for hemangioblastoma, 33% for retinal angioma, 3% for renal cell carcinoma, and 3% for pancreatic cysts. 6 members of the family (all deceased; 4 males, 2 females) had suspected VHL and 2 (males) of these were suspected to have had Pheo/PGL.

CasePresentingHPOs: HP:0009711 (Retinal capillary hemangioma)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0005584; HP:0002666; HP:0002668 (Renal cell carcinoma, Pheochromocytoma, Paraganglioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 9201016; 8239848 (no genetic information; only phenotypes)

SupplementalData: N/A

Variant: p.Y112H (c.334T>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 2222, https://www.ncbi.nlm.nih.gov/clinvar/variation/2222/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: Y112H (c.334T>C)

MultipleGeneVariants: N/A

PatientID: 13

KindredID: 354

Case: Sex unknown, Age unknown, French

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0002666; HP:0030405 (pheochromocytoma, pancreatic endocrine tumour)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0005584 (renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R167Q (c.500G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVar: 2216 https://www.ncbi.nlm.nih.gov/clinvar/variation/2216/

CAID: N/A

gnomAD: 0.000003977 https://gnomad.broadinstitute.org/variant/3-10191507-G-A

VariantEvidence:N/A

MutationType: missense_variant;transition

CivicName: R167Q (c.500 G >A)

MultipleGeneVariants: N/A

Among patients prospectively followed by the members of the French VHL Study Group, 35 consecutive patients with well-documented endocrine pancreatic tumour (20 women and 15 men; median age,37 [21Y-57] years) were included. The data from 7 patients with EPT have been partially reported previously in Hammel et al., 1995;2000. All 35 patients had VHL germline mutations and were assessed for the presence of pheochromocytoma and renal carcinoma in addition to pancreatic tumours. The presence of other phenotypes was not described. Patient no. 20 from family 900 had a frameshift mutation in the VHL gene (c.284delC) and presented with pancreatic endocrine tumour. The patients' phenotypes are highly specific to VHL disease (PP4) and frameshift mutation supports PM4.

GroupID/ KindredID: Family D

DiseaseAssertion: VHL (clinically diagnosed in, at minimum, the proband)

GroupSize: 2

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: Belgian

GroupAgeRange: 46-? (mean 46Y)

GroupInfo: 2 family members are grouped with this deletion

GroupPresentingHPOs: HP:0010797; HP:0009711; HP:0001737 (hemangioblastoma, retinal capillary hemangioma, pancreatic cysts)

GroupHPOFreeText: both (2) patients were found with hemangioblastoma, 1 with retinal capillary hemangioma, and 1 with pancreatic cysts. Unclear specific patient-phenotype grouping

GroupNotHPOs: HP:0005584; HP:0002666 (renal cell carcinoma, pheochromocytoma)

GroupNotHPOFreeText: No patients were found to have pheochromocytoma or RCC

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: Deletion of exon 1

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Southern blot analysis with EcoRI and hybridization with the g7 probe generated an aberrant restriction fragment (Fig. 3). This aberrant restriction fragment was recognized by probes representing exons 2 and 3. However, hybridization with the exon 1 probe resulted in a normal banding pattern, indicating a deletion encompassing exon 1.

MutationType: exon_loss_variant

CivicName: exon 1 deletion

MultipleGeneVariants: N/A

PatientID: 10

KindredID: 10

Case: F, 41Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: No family history of VHL.

CohortInfo: 26 Korean patients with more than one HAB in the CNS or eye, a single HAB in the CNS or retina plus a visceral manifestation (multiple renal, pancreatic or hepatic cysts, pheochromocytoma and RCC) and positive family history plus any one of the above manifestations.

CasePresentingHPOs: HP:0010797 (Hemangioblastoma)

CaseHPOFreeText: CNS hemangioblastoma. Diagnosed with VHL Type 1.

CaseNotHPOs: HP:0002666; HP:0009711; HP:0005584 (Pheochromocytoma, Retinal capillary hemangioma, Renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.E70K (c.208G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 43598, https://www.ncbi.nlm.nih.gov/clinvar/variation/43598/

CAID: N/A

gnomAD: 0.000004365, https://gnomad.broadinstitute.org/variant/3-10183739-G-A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: E70K (c.208G>A)

MultipleGeneVariants: N/A

PatientID: 3

KindredID: 3

Case: M, 55Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: No family history of VHL.

CohortInfo: 26 Korean patients with more than one HAB in the CNS or eye, a single HAB in the CNS or retina plus a visceral manifestation (multiple renal, pancreatic or hepatic cysts, pheochromocytoma and RCC) and positive family history plus any one of the above manifestations.

CasePresentingHPOs: HP:0010797 (Hemangioblastoma)

CaseHPOFreeText: Multiple or bilateral CNS hemangioblastoma. Diagnosed with VHL Type 1. Phenotypes revised from previous reports (see “PreviouslyPublished” section below for PMID).

CaseNotHPOs: HP:0002666; HP:0009711; HP:0005584 (Pheochromocytoma, Retinal capillary hemangioma, Renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 19270817

SupplementalData: N/A

Variant: p.E70K (c.208G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 43598, https://www.ncbi.nlm.nih.gov/clinvar/variation/43598/

CAID: N/A

gnomAD: 0.000004365, https://gnomad.broadinstitute.org/variant/3-10183739-G-A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: E70K (c.208G>A)

MultipleGeneVariants: N/A

PatientID: 37

KindredID: F01

Case: F, Age Unknown, Unknown Ethnicity

DiseaseAssertion: Asymptomatic

FamilyInfo: A total of 12 members of this family (F01) had a complete deletion of the VHL gene. Five of these patients (16, 18, 21, 33, 43) presented with clinical features of VHL. This family was previously published except for patients 43 and 48 which were newly diagnosed with VHL disease in the current study.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 17537157

SupplementalData: Figure 2.

Variant: Complete Deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Deletion of ~250.9kb resulted in deletion of the VHL gene.

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PMID: 20567917

Gene: VHL

StandardizedReferenceSequence: NM_000551.3

PatientID: 3

KindredID: A

Case: Sex Unknown, 35Y0M, Mexican (Latino/Admixed American)

DiseaseAssertion: assumed VHL

FamilyInfo: two other symptomatic and one asymptomatic members of family A had this mutation. The symptomatic individuals had cerebellar hemangioblastomas, as well as spinal hemangioblastomas snd renal cysts.

CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

CaseHPOFreeText: Symptomatic before 29Y, clinically manifested as >3 cerebellar hemangioblastomas

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 20064270

SupplementalData: N/A

Variant: p.F76del (c.227_229del)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA357012 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.226_228delTTC

gnomAD: N/A

VariantEvidence: N/A

MutationType: inframe_deletion

CivicName: F76del (c.227_229del)

MultipleGeneVariants: N/A

PatientID: 13

KindredID: C

Case: Sex Unknown, 17Y0M, Mexican (Latino/Admixed American)

DiseaseAssertion: asymptomatic

FamilyInfo: At least 13 members in this family presented with the mutation. 5 were asymptomatic (ages 9, 12, 13, 17, and 29Y). Other family manifestations include: cerebellar, spinal, retinal HBs, pancreatic, hepatic, suprarenal and kidney cysts, epididymal cystadenoma, and RCC. Fig 1 displays family pedigree.

CasePresentingHPOs: N/A

CaseHPOFreeText: Patient was asymptomatic at the time, likely due to young age

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 20064270 (Here, the family cohort is given with a reportedly different variant of: p.G34Rfs*98 (c.99_100insA). Unclear of why this is or which most correctly corresponds to the family).

SupplementalData: N/A

Variant: p.G34Rfs*98 (c.99_100insA)

LegacyVariant: c.1012_1013insA

CaseProblemVariantFreeText: The ‘1012_1013insA’ mutation is out-of-frame, leading to a modification of 31 amino acids downstream and a premature stop codon at nucleotides 5441-5443 (amino acid residue 131).

ClinVarID: N/A

CAID: CA2018007671 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2018007671

gnomAD: N/A

VariantEvidence: The modified amino acids are located in a domain common to all pVHL isoforms, the highly conserved cctbinding domain of the protein, involved in the formation of the pVHL elongin complex that is crucial for tumor suppression. Furthermore, the mutant protein is prematurely truncated and lacks the C-terminal half of exon 2 and exon 3 completely, which includes the nuclear export signal and the elongin C binding site of pVHL. Thus, this truncated protein would affect the two functional isoforms of pVHL: the major isoform pVHL30 and pVHL19, but not isoform 2, which lacks exon 2 but is not functional

MutationType: plus_1_frameshift_variant

CivicName: G34Rfs (c.99_100insA)

MultipleGeneVariants: N/A

PatientID: III-3

KindredID: 3

Case: M, Age Unknown (deceased), Chinese

DiseaseAssertion: CNS Hemangioblastoma

FamilyInfo: The transition mutation was found and confirmed in 1 patient (II-3) and 2 carriers (III-7, IV-2). 5 members, including III-3, had hemangioblastomas of the CNS, but had all passed away before genetic testing. Could be assumed and deduced the genetics due to pedigree showing future linear relations of this mutation.

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.L116V (c.346C>G) [assumed]

LegacyVariant: p.L116V (c.559C>G) [assumed]

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351753642 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.346C%3EG

gnomAD: N/A

VariantEvidence: No genetic testing was done prior to death, however family history and presentation leads to this deduction

MutationType: missense_variant;transversion

CivicName: L116V (c.346C>G)

MultipleGeneVariants: N/A

GroupID: 10

DiseaseAssertion: assumed VHL

GroupSize: 6

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: Chinese

GroupAgeRange: 47.0Y +/- 18.4Y

GroupInfo: Clinical characteristics of 258 patients from 80 unrelated Chinese families were reported in this study. Grouped by the 21 mutations found, 2 families with 6 members total were described, and phenotypic information was given for this group.

GroupPresentingHPOs: HP:0010797; HP:0009711; HP:0005584; HP:0001737; HP:0009715 (hemangioblastoma, retinal capillary hemangioma, renal cell carcinoma, pancreatic cysts, papillary cystadenoma of the epididymis)

GroupHPOFreeText: 3 of the 6 members presented with CNS hemangioblastoma (mean age of 40.0Y), 3/6 had retinal capillary hemangiomas (at a mean age of 23Y), renal cell carcinoma in 3 members (at a mean age of 35.3Y), pancreatic cysts in 2 members (with age of onsets of 26 and 27Y), and 1 with a papillary cystadenoma of the epididymis genital system tumor (epididymis or broad ligament) (at age 18Y).

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: no members were found with pheochromocytomas

GroupPreviousTesting: N/A

PreviouslyPublished: 29330336

SupplementalData: N/A

Variant: p.R113* (c.337C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 220414 https://www.ncbi.nlm.nih.gov/clinvar/variation/220414/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: R113* (c.337C>T)

MultipleGeneVariants: N/A

PatientID: I.1

KindredID: F10

Case: M, Age Unknown, Ethnicity Unknown

DiseaseAssertion: Asymptomatic

FamilyInfo: This patient’s partner and two children were all carriers of the D143= (c.429C>T) germline VHL variant. Their son was diagnosed with splenomegaly and polycythemia and was homozygous for the variant. All other family members were asymptomatic.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.D143= (c.429C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 416990, https://www.ncbi.nlm.nih.gov/clinvar/variation/416990/

CAID: N/A

gnomAD: 0.000007953, https://gnomad.broadinstitute.org/variant/3-10188286-C-T?dataset=gnomad_r2_1

VariantEvidence: N/A

MutationType: missense_variant;transition; synonymous_variant

CivicName: D143= (c.429C>T)

MultipleGeneVariants: N/A

PatientID: 5

KindredID: 5

Case: M, 10Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: (See figure 3E for pedigree). The proband (Patient 5's) mother had left adrenal pheochromocytomas, and his grandmother had bilateral adrenal pheochromocytomas.

CasePresentingHPOs: HP:0006748 (adrenal pheochromocytoma)

CaseHPOFreeText: Proband presented with bilateral adrenal pheochromocytoma

CaseNotHPOs:None

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Y98C (c.293A>G)

LegacyVariant: N/A

CaseProblemVariant Free Text: N/A

ClinVar: 223176, https://www.ncbi.nlm.nih.gov/clinvar/variation/223176/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_transition

CivicName: Y98C (c.293A>G)

MultipleGeneVariants: N/A

PMID: 31016171

Gene: VHL

StandardizedReferenceSequence: NM_000551.3

GroupID/ KindredID: 4783NCI

DiseaseAssertion: VHL

GroupSize: N/A

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: Two germline familial VHL mutations were associated with this family. They were: c.382C>T and c.381G>T and this data was taken from the National Cancer Institute database. It is unclear how many members belonging to Family ID 4783NCI had both mutations. Table 4 lists all ID and mutations associated with individuals with pheochromocytoma.

GroupPresentingHPOs: HP:0002666 (pheochromocytoma)

GroupHPOFreeText: Described as a VHL family with pheochromocytoma. Other phenotypes are likely, including renal cell carcinoma, however not detailed here.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G127G (c.381G>T)

LegacyVariant: p.G127G (c.594G>T)

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA432421824 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.381G>T

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion; synonymous_variant

CivicName: G127G (c.381G>T)

MultipleGeneVariants: Germline, VHL, c.382C>T (p.Leu128Phe)

GroupID: 9

DiseaseAssertion: Neuroendocrine neoplasm (pheochromocytoma or paraganglioma)

GroupSize: 3

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: Ethnicity unknown

GroupAgeRange: N/A

GroupInfo: This mutation (p.R167W (c.499C>T)) was found in 3 patients, 2 with a family history and/or a syndromic presentation, and 1 patient with an apparently sporadic presentation.

GroupPresentingHPOs: HP:0100634 (Neuroendocrine neoplasm)

GroupHPOFreeText: Patients with a pheochromocytoma or a functional paraganglioma were recruited from several different French clinical centers participating in several clinical research networks (Cortico et Medullosurrènale: les Tumeurs Endocrines, Paragan-Glioma Network, Groupe des Tumeurs Endocrines)

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: RET, NF1, SDHB/SDHC/SDHD

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R167W (c.499C>T)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

CAID: N/A

gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: R167W (c.499C>T)

MultipleGeneVariants: N/A

ArticleReferenceSequence: Not specified – Assumption: variants assumed to have been documented by the author under reference sequence NM_000551.3

GenotypingMethod: Three coding exons and flanking introns of VHL were amplified by PCR, followed by direct sequencing to detect missense and splice mutations. MLPA was used to detect large exon deleteions.

SamplingMethod: peripheral blood

GroupID/ KindredID: 7

DiseaseAssertion: VHL

GroupSize: 2

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: Polish

GroupAgeRange: N/A

GroupInfo: Familial VHL stated; 2 family members recorded with this mutation.

GroupPresentingHPOs: HP:0009711; HP:0010797 (retinal capillary hemangioma, hemangioblastoma)

GroupHPOFreeText: 1 patient was tallied with a retinal capillary hemangioma and both (2) with cHemangioblastomas.

GroupNotHPOs: HP:0005584 (renal cell carcinoma)

GroupNotHPOFreeText: None of the patients were recorded to have RCC

GroupPreviousTesting: N/A

PreviouslyPublished: 32179488

SupplementalData: N/A

Variant: p.F76del (c.226_228delTTC)

CaseProblemVariantFreeText: NM_000551.3:c.226_228delTTC automaps to updated c.227_229delTCT

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA357012 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.226_228delTTC

gnomAD: N/A

VariantEvidence: N/A

MutationType: inframe_deletion

CivicName: F76del (c.227_229del)

MultipleGeneVariants: N/A

PatientID: 1

KindredID: 1

Case: F, 29Y0M, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: Negative family history, suggesting a de novo mutation.

CasePresentingHPOs: HP:0010797; HP:0002858; HP:0012503; HP:0000141 (hemangioblastoma; meningioma; pituitary lesion; amenorrhea)

CaseHPOFreeText: 1-year history of amenorrhea, she was found to have a brainstem hemangioblastoma, posterior fossa meningiomas and a pituitary spaceoccupying lesion causing hyperprolactinemia. Complete resection of the brainstem hemangioblastoma and posterior fossa meningiomas was achieved in one single operation via a sub-occipital posterior combined with retrosigmoid approach. The patient was later discharged without obvious postoperative complications.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: Partial deletion of Exon 1

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: deletion

CivicName: N/A

MultipleGeneVariants: N/A

PatientID: P7

KindredID: 4

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: pheochromocytoma

FamilyInfo: N/A

CasePresentingHPOs: HP:0002666 (pheochromocytoma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Y98H (c.292T>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVar: 2223 https://www.ncbi.nlm.nih.gov/clinvar/variation/2223/

CAID: N/A

gnomAD: 0.00001343 https://gnomad.broadinstitute.org/variant/3-10183823-T-C

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: Y98H (c.292T>C)

MultipleGeneVariants: N/A

PatientID: None (Brother 1)

KindredID: 1

Case: M, 79Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: FamilyInfo: One brother (proband, 75Y) presented with Hemangioblastoma, Hypertension, Cataract, Visual loss, Amblyopia, Diabetes mellitus, Adenocarcinoma of the colon, Clear cell renal cell carcinoma, Retinitis, Anal canal adenocarcinoma, Spinal hemangioblastoma, Gastrointestinal carcinoma, Cerebellar hemangioblastoma and the same VHL mutation as this patient. Mother with a brain tumor of unconfirmed pathology, and another brother (70Y) with renal cell carcinoma with the VHL gene mutation. Nephew (44Y) has VHL mutation but is asymptomatic. Niece (40Y) had a brain hemorrhage, other niece had hematologic malignancy, son has pancreatic cancer; genetic information is unclear or not provided for either.

CasePresentingHPOs: HP:0005584 (Renal cell carcinoma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Figure 1

Variant: p.E70K (c.208G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 43598, https://www.ncbi.nlm.nih.gov/clinvar/variation/43598/

CAID: N/A

gnomAD: 0.000004365, https://gnomad.broadinstitute.org/variant/3-10183739-G-A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: E70K (c.208G>A)

MultipleGeneVariants: N/A

PatientID: Carrier 7 (niece to proband 3)

KindredID: 1

Case: M, Age Unknown, Chinese

DiseaseAssertion: Asymptomatic

FamilyInfo: The family with PCCs includes 56 members of 4 generations, and is from Gansu Province. Among them, 7 extended over 3 generations were diagnosed as PCCs. One died before admission and another died due to a cardiovascular incident. Five were initially evaluated; evaluation included medical history, physical examination, abdominal ultrasonography, CT or MRI and laboratory tests. All 5 probands of this family underwent surgical resection. The tumors were benign under pathological examinations. There were no recurrence and malignant transformation over the period of up to 23-year follow-up. Twenty members, including 5 live patients and 15 direct relatives, accepted genetic examination.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.H125P (c.374A>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223201, https://www.ncbi.nlm.nih.gov/clinvar/variation/223201/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: H125P (c.374A>C)

MultipleGeneVariants: N/A

PatientID: 19

KindredID: 19

Case: F, 72Y0M, Ethnicity Unknown

DiseaseAssertion: Adrenal pheochromocytoma

FamilyInfo: N/A

CasePresentingHPOs: HP:0006748 (Adrenal pheochromocytoma)

CaseHPOFreeText: Unilateral benign adrenal pheochromocytoma that was operated on at age 58.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.I147T (c.440T>C)

LegacyVariant: I147T (c.653T>C)

CaseProblemVariantFreeText: N/A

ClinVarID: 411964, https://www.ncbi.nlm.nih.gov/clinvar/variation/411964/

CAID: N/A

gnomAD: N/A

VariantEvidence: Variant reported as I147T (c.653T>C), legacy nomenclature (AF010238.1), and was mapped to p.Ile147Thr (c.440T>C) in accordance with reference sequence NM_000551.3.

MutationType: missense_variant;transition

CivicName: I147T (c.440T>C)

MultipleGeneVariants: N/A

GroupID: 19A

Case: Sex, Age, Ethnicity unknown

DiseaseAssertion: VHL

FamilyInfo: None. The patient with the given mutation in this study was a VHL patient with pancreatic ICTs.

CasePresentingHPOs: HP:0030405 (pancreatic endocrine tumor)

CaseHPOFreeText: Patient has islet cell tumors (ICTs), or listed as pancreatic endocrine tumor.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Y156C (c.467A>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 43600 https://www.ncbi.nlm.nih.gov/clinvar/variation/43600/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: Y156C (c.467A>G)

MultipleGeneVariants: N/A

KindredID: 99

GroupID: 30

GroupSize: Unknown

GroupNumberMales: Unknown

GroupNumberFemales: Unknown

GroupEthnicity: Unknown

GroupAgeRange: Unknown

DiseaseAssertion: VHL

GroupInfo: Kindred no. 99 describes a family where at least one member (unspecified how many) had this mutation in the VHL gene. No phenotypic information is listed for this kindred.

GroupPresentingHPOs: N/A

GroupHPOFreeText: No phenotypic information is listed for this kindred.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: L153Cfs*6 (c.457del)

LegacyVariant: p.224fs (c.670delC)

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA432421920

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: L153fs (c.457delC)

MultipleGeneVariants: N/A

ArticleReferenceSequence: Not specified – Assumption: variants assumed to have been documented by the author under reference sequence NM_000551.3

GenotypingMethod: realtime quantitative PCR (RQ-PCR) was used to detect large deletions in the VHL gene. RQ-PCR assay was done using SYBR green master mix for detecting large deletions in the VHL gene.

SamplingMethod: peripheral venous blood

Case#: 4, Male, Han Chinese

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0001249, HP:0007957, HP:0001433 (Mental Retardation (severe), Corneal Clouding, Hepatosplenomegaly)

CaseHPOFreeText: Skeletal Deformities

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0 Leukocyte IDUA activity (nmol/h/mg protein) (isolated leukocytes in the latter)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Using the artificial substrate 4-methyl-umbelliferyl α-L-iduronide (Sigma)

Variant1: c.792+1G>T

Variant1ClinVarID: N/A

Variant1CAID: CA355962278

Variant2: c.792+1G>T

Variant2ClinVarID: N/A

Variant2CAID: CA355962278

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 1, Male, Han Chinese

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0001249, HP:0007957, HP:0001433 (Mental Retardation (severe), Corneal Clouding, Hepatosplenomegaly)

CaseHPOFreeText: Skeletal Deformities

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0 Leukocyte IDUA activity (nmol/h/mg protein) (isolated leukocytes in the latter)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Using the artificial substrate 4-methyl-umbelliferyl α-L-iduronide (Sigma)

Variant1: c.1190-1G>A

Variant1ClinVarID: 1204494

Variant1CAID: CA355963511

Variant2: Not Identified

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 4, 11 years old, Iranian

DiseaseAssertion: MPS1-H (Severe)

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity not detected

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1029C>A (p.Y343X)

Variant1ClinVarID: 222997

Variant1CAID: CA356984

Variant2: c.1029C>A (p.Y343X)

Variant2ClinVarID: 222997

Variant2CAID: CA356984

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 3, 4 years old, Iranian

DiseaseAssertion: MPS1-H (Severe)

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity not detected

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: P13, Female, 2.7 years (diagnosed), 5.1 (report), 18 kg (weight), 96 cm (height), Algerian

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Parents are not consanguineous

CasePresentingHPOs: HP:0001249, HP:0001999, HP:0000943, HP:0001387, HP:0002240, HP:0001387, HP:0007957, HP:0000238 (Mental Retardation, Facial Dysmorphic Features, Multiple Dysostosis, Joint Stiffness, Hepatomegaly, Hernia(Ombelical), Corneal Opacity, Hydrocephalus)

CaseHPOFreeText: Chronic Rhinorrhea

CaseNotHPOs: N/A

CaseNotHPOFreeText: Cardiac Manifestations

CaseEnzymeAssay: IDUA Enzyme activity 2 (% to the reference range mean)

CaseUrineGAGs: GAG quantitation 19.6 (fold change to the reference range mean according to age)

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Direct DNA Fragments Sequencing

Variant1: c.501C>G (p.Tyr167*)

Variant1ClinVarID: 92644

Variant1CAID: CA220511

Variant2: c.501C>G (p.Tyr167*)

Variant2ClinVarID: 92644

Variant2CAID: CA220511

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 17 (see Table 2), 40 weeks (Gestational age)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1205G>A (p.W402X)

Variant2ClinVarID: 11908

Variant2CAID: CA220498

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 2 (see Table 2), 38 weeks, 1 day (Gestational age)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Inguinal hernia (HP:0000023)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: Upper respiratory tract involvement

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.208C>T (p.Q70X)

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 7 (see Table 2), 33 weeks, 1 day (Gestational age)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.44 nmol x mg-1 × hr-1

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.653T>C (p.L218P)

Variant2ClinVarID: 222995

Variant2CAID: CA356986

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 29 (see Table 2), 40 weeks, 5 days (Gestational age)

DiseaseAssertion: MPS1-S

FamilyInfo: Sibling of Patient 28 (see Table 2)

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: Upper respiratory tract involvement

CaseEnzymeAssay: 1.61 nmol x mg-1 × hr-1

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.474-2A>G (new nomenclature: c.386-2A>G)

Variant1ClinVarID: 222994

Variant1CAID: CA356991

Variant2: c.1148G>A (p.R383H)

Variant2ClinVarID: 558189

Variant2CAID: CA:2802205

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 23837464

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient 20 (see Table 2), 37 weeks, 1 day (Gestational age)

DiseaseAssertion: MPS1-H/S

FamilyInfo: Sibling of Patient 19 (see Table 2)

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: Upper respiratory tract involvement

CaseEnzymeAssay: 0.95 nmol x mg-1 × hr-1

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1044C>A (p.N348K)

Variant2ClinVarID: N/A

Variant2CAID: CA:355963142

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 9 (see Table 2), 37 weeks, 2 days (Gestational age)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Upper respiratory tract involvement

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.653T>C (p.L218P)

Variant2ClinVarID: 222995

Variant2CAID: CA:356986

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Subject 1, female, in her 30s (age at enrollment), died during extension study from pneumonia and respiratory failure sixty-five days after her first dose in the extension study.

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs: HP:0002093, HP:0002540, HP:0002090, HP:0002176 (Chronic respiratory insufficiency, inability to walk, pneumonia, spinal cord compression)

CaseHPOFreeText: Hemidiaphragmatic paralysis, improved strength and range of motion

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes - Enzyme replacement therapy with laronidase

CaseBMT: N/A

Variant1: N/A

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: II-2, Female, 2 years (onset), Chinese

DiseaseAssertion: MPS 1

FamilyInfo: I-1 and I-2 are the parents, II-4 is a full sibling of II-2 and a full child of I-1 and I-2. II-4 also carries the disease. (pedigree is figure # 1).

CasePresentingHPOs: HP:0001367, HP:0000622, HP:0007663, HP:0001718, HP:0001643, HP:0001698, HP:0000238, (Abnormal joints, Blurred vision, Decreased vision, Mitral stenosis (severe), Patent ductus arteriosus (tubular), Pericardial effusion (moderate), Hydrocephalus)

CaseHPOFreeText: Abnormal mitral valve development, Anterior mitral valve prolapses and insufficiency (moderate), Pulmonary hypertension (moderate), Bilateral temporal arachnoid cyst, Congenital spinal stenosis, Congenital glaucoma, Corneal gray degeneration, Corneal staphyloma

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Sanger Sequencing

Variant1: c.1037T>G

Variant1ClinVarID: 11927

Variant1CAID: CA256128

Variant2: c.18115dupT

Variant2ClinVarID: 1454082

Variant2CAID: CA2573137507

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Patient D4, Druze religious group, located in lower Galilee.

DiseaseAssertion: N/A

FamilyInfo: May have relation with Patient D5 due to being located in the same village. Parents were found to be heterozygous for the mutation.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1096A>C (p.T366P)

Variant1ClinVarID: 11916

Variant1CAID: CA:256117

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 8328452

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient M3, Muslim religious group, located in Gaza. The cells of the patient were listed in the catalog of the Human Genetic Mutant Cell Repository as "Hurler/Scheie". However, the patient at age 6 years had been described as having a typical MPS1-H phenotype except for apparently normal intelligence (measured across a language barrier).

DiseaseAssertion: MPS1-H/S or MPS1-H

FamilyInfo: Parents were found to have both mutations were found in heterozygous form in the DNA. Affected brother deceased at age 9.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1225G>A (p.G409R)

Variant1ClinVarID: 1084956

Variant1CAID: CA91169920

Variant2: (p.X654C)

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient D1, Druze religious group, located in lower Galilee.

DiseaseAssertion: MPS1-H

FamilyInfo: Both parents, as well as an aunt and uncle who had a deceased affected child, were heterozygous for the same mutation.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.192C>A (p.Y64X)

Variant1ClinVarID: 11914

Variant1CAID: N/A

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 19, Female, infancy (onset), 3 years (diagnosed), 17 years (report)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: N/A

CasePresentingHPOs: HP:0004322, HP:0001387, HP:0002240, HP:0001744, HP:0001537, HP:0001007, HP:0000158, HP:0000280, HP:0000943, HP:0007957 (Short Stature, Joint Stiffness, Hepatomegaly (severe), Splenomegaly(severe), Umbilical Hernia, Hirsutism, Large Tongue, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: (Mental Development (delayed), Systolic murmur 3/6/combined defect of mitral valve)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.H539T (fsX21)

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: c.1650+5G>A (splicing error)

Variant2ClinVarID: 92634

Variant2CAID: CA220504

AdditionalVariants: p.A8, p.A20, p.Q33H

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 18, Male, 15 years (onset), 15 years (diagnosed), 15 years (report)

DiseaseAssertion: Scheie Syndrome

FamilyInfo: Patients 17 and 18 are siblings

CasePresentingHPOs: HP:0004322, HP:0001387, HP:0002240, HP:0001744, HP:0001537, HP:0000280, HP:0000943 (Short Stature, Joint Stiffness, Hepatomegaly (moderate), Splenomegaly(mild), Umbilical Hernia, Coarse Facial Features (mild), Dysostosis Multiplex)

CaseHPOFreeText: (Mental Development (developmental quotient 93 at 15y, Verbal IQ 77; CIQ 79), Umbilical/Carpal Tunnel Syndrome)

CaseNotHPOs: HP:0000256 (Macrocephaly)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.Q380R

Variant1ClinVarID: 550799

Variant1CAID: CA2802202

Variant2: p.Q380R

Variant2ClinVarID: 550799

Variant2CAID: CA2802202

AdditionalVariants: p.A8/A8, p.A20/A20

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 7, Female, 8 months (onset), 10 months (diagnosed), 5 years (report)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0000256, HP:0001387, HP:0002240, HP:0001537, HP:0000486, HP:0002857, HP:0012185, HP:0000280, HP:0000943, HP:0007957 (Macrocephaly (at 8m), Joint Stiffness (at 8m), Hepatomegaly (Severe before HSCT, mild after HSCT), Umbilical Hernia, Strabismus, genua valga, carpal tunnel syndrome, Coarse Facial Features (very mild), Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (developmental quotient 110 at 1y, Developmental quotient 115 at 5y), Normal psychomotor development, Hearing problems,

CaseNotHPOs: HP:0004322, HP:0001744 (Short Stature, Splenomegaly)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: normal IDUA activity in leucocytes (4 years after HSCT)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Hematopoietic Stem Cell Transplantation at 1y

GenotypingMethod: Not Provided

Variant1: p.W402X

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1650 + 5G > A

Variant2ClinVarID: 92634

Variant2CAID: CA220504

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 8, Male, 2, 5 years (onset), 3,5 months (diagnosed), 16 years (report)

DiseaseAssertion: Hurler-Scheie Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0000256, HP:0001387, HP:0002240, HP:0001744, HP:0001537, HP:001285, HP:0000280, HP:0000943, HP:0007957 (Macrocephaly, Joint Stiffness, Hepatomegaly (mild before HSCT), Splenomegaly (mild before HSCT), Umbilical Hernia, Carpal tunnel syndrome, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (Borderline developmental quotient at 3y, IQ 117 at 12y)

CaseNotHPOs: HP:0004322, HP:0002240, HP:0001744 (Short Stature, Hepatomegaly (after HSCT), Splenomegaly (after HSCT))

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: normal IDUA activity at 16 years

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Hematopoietic Stem Cell Transplantation at 5y

GenotypingMethod: Not Provided

Variant1: p.W402X

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: p.E640fs

Variant2ClinVarID: 558359

Variant2CAID: CA355966048

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 14, Male, 24 months (onset), 3 years (diagnosed), 8 years (report), deceased (at 9y)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0004322, HP:0000256, HP:0001387, HP:0002240, HP:0001744, HP:0001638, HP:0000023, HP:0002415, HP:0000158, HP:0000280, HP:0000943, HP:0007957 (Short Stature, Macrocephaly, Joint Stiffness, Hepatomegaly (severe), Splenomegaly (moderate), Cardiomyopathy (involvement of valves), Inguinal Hernia, Leukodystrophy (in MRI), Large Tongue, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: (Mental Development (Delayed since infancy), Vision and Hearing impairment, Ear Inflammations, Cervical Canal Stenosis (in MRI at 7y), Tracheostomy)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.Q70X

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: p.W626X

Variant2ClinVarID: 928997

Variant2CAID: CA355965968

AdditionalVariants: p.Q33H/Q33H, p.L118

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 19396826

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: 12, Female, 5 months (onset), 5 years (diagnosed), 5 years (report), deceased (at 7y)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0004322, HP:0000256, HP:0001387, HP:0002240, HP:0001744, HP:0001537, HP:0000365, HP:0000280, HP:0000943, HP:0007957 (Short Stature, Macrocephaly, Joint Stiffness, Hepatomegaly (Severe), Splenomegaly (moderate), Umbilical Hernia, Deafness (progressive), Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (Delayed)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.Q70X

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: p.D315Y

Variant2ClinVarID: N/A

Variant2CAID: CA355962740

AdditionalVariants: p.A8, p.A20, p.Q33H, p.L118

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 9, Female, 3-4 years (onset), 4 years (diagnosed), 20 years (report), deceased (accidentally at 21y)

DiseaseAssertion: Hurler-Scheie Syndrome

FamilyInfo: Not Provided

CasePresentingHPOs: HP:0000256, HP:0001387, HP:0002240, HP:0001744, HP:0001639, HP:001285, HP:0000158, HP:0000280, HP:0000943, HP:0007957 (Macrocephaly, Joint Stiffness (Severe and progressive), Hepatomegaly (Severe at diagnosis but none at report), Splenomegaly (mild at diagnosis and report), Hypertrophic Cardiomyopathy (Progressive), Carpal tunnel syndrome, Large Tongue, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: Mental Development (Uneven Development at 2y; IQ 117 at 12y)

CaseNotHPOs: HP:0004322 (Short Stature)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: ERT since 18y

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.W402X

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: p.E640fs

Variant2ClinVarID: 558359

Variant2CAID: CA355966048

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 20, Female, infancy (onset), 2 years (diagnosed), 2 years (report)

DiseaseAssertion: Hurler Syndrome

FamilyInfo: N/A

CasePresentingHPOs: HP:0004322, HP:0002240, HP:0001744, HP:0000280, HP:0000943, HP:0007957 (Short Stature, Hepatomegaly, Splenomegaly, Coarse Facial Features, Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: (Mental Development (delayed since early infancy), Mild LV hypertrophy, Frequent respiratory infections, Vision Impairment and Hearing Loss)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

GenotypingMethod: Not Provided

Variant1: p.V620F

Variant1ClinVarID: 1067173

Variant1CAID: CA355965934

Variant2: p.V620F

Variant2ClinVarID: 1067173

Variant2CAID: CA355965934

AdditionalVariants: p.R105Q/R105Q, p.N181/N181, p.A314/A314, p.A361T/A361T, p.T388/T388, p.T410/T410, p.V454I/V454I, p.R489/R489

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 55, 6 months old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, dysostosis multiplex (HP:0000280, HP:0001433, HP:0000943)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.7% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.589G>A (p.Gly197Ser)

Variant1ClinVarID: 1526094

Variant1CAID: CA355961839

Variant2: c.1091C>T (p.Thr364Met)

Variant2ClinVarID: 11925

Variant2CAID: CA256126

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 16, 2 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, corneal clouding, recurrent infections, dysostosis multiplex, intellectual disability, hernia (HP:0000280, HP:0001433, HP:0002828, HP:0007957, HP:0002719, HP:0000943, HP:0001249, HP:0100790)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 3.3% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.568_581del (p.Asn190Hisfs*204)

Variant1ClinVarID: 3639714

Variant1CAID: CA2801994

Variant2: c.568_581del (p.Asn190Hisfs*204)

Variant2ClinVarID: 3639714

Variant2CAID: CA2801994

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 5, 2 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, corneal clouding, recurrent infections, dysostosis multiplex (HP:0000280, HP:0001433, HP:0007957, HP:0002719, HP:0000943)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.2% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.343G>T (p.Asp115Tyr)

Variant1ClinVarID: N/A

Variant1CAID: CA355961128

Variant2: c.343G>T (p.Asp115Tyr)

Variant2ClinVarID: N/A

Variant2CAID: CA355961128

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 21, 2 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, recurrent infections (HP:0000280, HP:0001433, HP:0002719)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.9% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.935G>A (p.Trp312Ter)

Variant1ClinVarID: N/A

Variant1CAID: CA355962697

Variant2: c.935G>A (p.Trp312Ter)

Variant2ClinVarID: N/A

Variant2CAID: CA355962697

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 11, 4 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: Sibling of patient 10

CasePresentingHPOs: Coarse facial features, recurrent infections, dysostosis multiplex, intellectual disability, hernia (HP:0000280, HP:0002719, HP:0000943, HP:0001249, HP:0100790)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 3.6% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.531C>G (p.Phe177Leu)

Variant1ClinVarID: 2432729

Variant1CAID: CA2801983

Variant2: c.531C>G (p.Phe177Leu)

Variant2ClinVarID: 2432729

Variant2CAID: CA2801983

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 39, 1 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Joint contractures, dysostosis multiplex (HP:0002828, HP:0000943)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 3.4% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1373T>C (p.Leu458Pro)

Variant1ClinVarID: N/A

Variant1CAID: CA355964255

Variant2: c.1373T>C (p.Leu458Pro)

Variant2ClinVarID: N/A

Variant2CAID: CA355964255

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 53, 2 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, corneal clouding, recurrent infections, intellectual disability, hernia (HP:0000280, HP:0001433, HP:0007957, HP:0002719, HP:0001249, HP:0100790)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.5% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.502G>T (p.Gly168Ter)

Variant1ClinVarID: N/A

Variant1CAID: CA355961652

Variant2: c.1402+1G>A

Variant2ClinVarID: 555490

Variant2CAID: CA355964379

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 19, 1 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, corneal clouding, recurrent infections, dysostosis multiplex, hernia (HP:0000280, HP:0001433, HP:0002828, HP:0007957, HP:0002719, HP:0000943, HP:0100790)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.7% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.784delC (p.His262Thrfs*55)

Variant1ClinVarID: 956890

Variant1CAID: CA2802083

Variant2: c.784delC (p.His262Thrfs*55)

Variant2ClinVarID: 956890

Variant2CAID: CA2802083

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 49, 2 years old (age at report), male, Indian