Case#:Not assigned

DiseaseAssertion:MPS type I with evidence of cognitive impairment defined as a score of at least 1 SD below mean on IQ testing or in one domain of neuropsychological function; attenuated MPS I

FamilyInfo:No information

CasePresentingHPOs:HP:0100543

CaseHPOFreeText:

CaseNotHPOs:HP:0032557

CaseNotHPOFreeText:Subjects were excluded if they had undergone hematopoietic stem cell transplantation, were unable to comply with study procedures, had significant lumbar pathology precluding access to the intrathecal space via lumbar puncture, or significantly impaired spinal CSF flow as detected on a nuclear medicine flow study as part of screening.

CaseEnzymeAssay:No information

CaseUrineGAGs:No information

CaseERT:Yes

CaseBMT:No (exclusion criterion)

Variant1:Q70X

Variant1ClinVarID:

Variant1CAID:

Variant2:Q380R

Variant2ClinVarID:550799

Variant2CAID:

AdditionalVariants:N/A

ParentalGenotype:Not specified

PreviouslyPublished

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#: 17, Female, 9 years (onset), 10 years (diagnosed), 10 years (report)

DiseaseAssertion: Scheie Syndrome

FamilyInfo: Patients 17 and 18 are siblings

CasePresentingHPOs: HP:0004322, HP:0002240, HP:0001537, HP:0000280, HP:0000943, HP:0007957 (Short Stature, Hepatomegaly (moderate), Umbilical Hernia, Coarse Facial Features (mild), Dysostosis Multiplex, Corneal Clouding)

CaseHPOFreeText: (Mental Development (Verbal IQ 92; Performance IQ 84; CIQ 86), Mild septal hypertrophy; mitral valve dysplasia)

CaseNotHPOs: HP:0000256, HP:0001387, HP:0001744 (Macrocephaly, Joint Stiffness, Splenomegaly)

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#: Patient 9 (see Table 2), male, 12.7 years old (age at report), 7 years (duration of treatment), 7 surgeries

DiseaseAssertion: MPS1-HS

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs: HP:0000238, HP:0002176, HP:0002360 (Hydrocephalus, spinal cord compression, sleep abnormality)

CaseNotHPOFreeText: Shunt placement, psychiatric problems

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: Yes

CaseBMT: N/A

Variant1: c.1139A>G (p.Q380R)

Variant1ClinVarID: 550799

Variant1CAID: CA2802202

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

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Functional assay variant with a clinical significance of pathogenic.

DiseaseAssertion: MPS-I

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.1139A>G (p.Q380R)

Variant1ClinVarID: 550799

Variant1CAID: CA2802202

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: Q380R

Variant1ClinVarID: 550799

Variant1CAID: CA2802202

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Family 23, UK

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: The α-L-iduronidase enzyme activities in leucocytes from all patients in the study was measured using the artificial substrate 4-methylumbelliferyl α-L iduronide (Sigma). Values ranged from 0 to 2.47 nmol/h/mg protein (reference range: 28–92 nmol/h/mg protein) and did not correlate to the clinical phenotype.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1139A>G (p.Q380R)

Variant1ClinVarID: 550799

Variant1CAID: CA2802202

Variant2: c.1861C>T (p.R621X)

Variant2ClinVarID: 11917

Variant2CAID: CA256118

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A