1. Last 7 days
    1. 2/a

      Case#: 2/a, age 20, age 14 (report)

      DiseaseAssertion: Pompe Disease

      FamilyInfo: Family 2, no further information

      CasePresenting HPOs:HP:0002878, HP:0012378, HP:0003546, HP:0001324 (Respiratory failure, fatigue, exercise intolerance, muscle weakness)

      CaseHPOFreeText: valvular myopathy, biopsy with vacuolar myopathy with PAS +

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: single gene sequencing/analysis, 64.47 NaG/AaGIA, 92.28% inhibition of GAA; NaG/AaGIA above 40 and %INH above 87 are in the affected range

      Variants:

      Variant 1:NM_000152.5(GAA):c.377G>A (p.Trp126Ter)

      ClinVar: 932904

      Variant 2: NM_000152.5(GAA):c.1655T>C (p.Leu552Pro)

      ClinVar: 279811

      ParentalGenotypes: N/A

      PreviouslyPublished: N/A

    1. P10a

      Patient10: Female, 75yo

      CasePresentingHPOs: HP:0000822

      HPOsFreeText: LOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: 5yr follow-up MRI, 40yr disease duration, ERT lasted 103mo

      CasePMIDs: PMID: 25614309

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NC_000017.11:g.(?80118193)(80118357_?)del (del exon 18)

      ClinVar: 456368, https://www.ncbi.nlm.nih.gov/clinvar/variation/456368/

      gnomAD: n/a

    1. PD/VOUS-2

      CasePD/VOUS-2: 2 weeks diagnosis

      HPOsFreeText: GAA activity 16.6 (nmol · h−1 · mg−1), Mean percentage of normal 23.3%

      GenotypingMethod: Newborn Screening Panels


      Variant1: NM_000152.4:c.1726G>A (p.Gly576Ser)

      ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

      gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A


      Variant2: NM_000152.4:c.2065G>A (p.Glu689Lys)

      ClinVar: 4030 https://www.ncbi.nlm.nih.gov/clinvar/variation/4030/

      gnomAD: East Asian 0.2355, Overall 0.05524 http://gnomad.broadinstitute.org/variant/17-78087041-G-A


      Variant3: NM_000152.4:c.2069C>T (p.Pro690Leu)

      ClinVar: 424308 https://www.ncbi.nlm.nih.gov/clinvar/variation/424308/

      gnomAD: East Asian 1.077e-4, Overall 2.337e-5 http://gnomad.broadinstitute.org/variant/17-78087045-C-T


      CaseAddInfo: Patient has one pseudodeficency allele and one allele of uncertain significance, Nomenclature claims Variant 1 and 2 are in cis

    2. LOPD-14

      CaseLOPD-14: 2 weeks diagnosis

      HPOsFreeText: GAA activity 3.0 (nmol · h−1 · mg−1), Mean percentage of normal 4.2%

      GenotypingMethod: Newborn Screening Panels


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.2509C>T (p.Arg837Cys)

      ClinVar: 456408 https://www.ncbi.nlm.nih.gov/clinvar/variation/456408/

      gnomAD: European (Non-Finnish) 4.676e-5, Overall 2.487e-5 http://gnomad.broadinstitute.org/variant/17-78092019-C-T


      CaseAddInfo: Late Onset Pompe Disease

    1. c.2560C > T(p.Arg854*)

      Case21

      HPOsFreeText: See Group Phenotypes


      CasePreviousTesting: Sanger sequencing

      CaseMethod1: Sanger sequencing and PCR Amplification

      CaseMethod2: Whole Exome Sequencing (WES)

      CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.


      Variant1: NM_000152.4:c.2560C>T (p.Arg854*)

      ClinVar: 4034 https://www.ncbi.nlm.nih.gov/clinvar/variation/4034/

      gnomAD: African 1.891e-3, Overall 2.090e-4 http://gnomad.broadinstitute.org/variant/17-78092070-C-T


      Variant2: NM_000152.4:c.1129G>C (p.Gly377Arg)

      ClinVar: 497033 https://www.ncbi.nlm.nih.gov/clinvar/variation/497033/

      gnomAD: European (Non-Finnish) 2.356e-5, Overall 1.072e-5 http://gnomad.broadinstitute.org/variant/17-78082341-G-C


      CaseAddInfo: Infantile Onset Pompe Disease

    1. PD04

      Patient4: Female, southern China

      CasePresentingHPOs:

      HPOsFreeText: IOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo:

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.1935C>A (p.Asp645Glu)

      ClinVar: 4029, https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

      gnomAD: 0.0001721, http://exac.broadinstitute.org/variant/17-78086721-C-A

      Variant2: NM_000152.4(GAA):c.2185delC (p.Leu729Trpfs) **this is not the same protein transcript listed in paper (p.Thr729fsX8) but I could not find this in clinvar or allele registry)

      ClinVar: 370552, https://www.ncbi.nlm.nih.gov/clinvar/variation/370552/https://www.ncbi.nlm.nih.gov/clinvar/variation/370552/

      gnomAD: n/a

    1. P2

      PatientF3P2: Female, 36 years diagnosis, European and Native American

      CasePresentingHPOs: HP:0003236, HP:0012378, HP:0003547, HP:0009113, HP:0002910 (Increased serum CK, Fatigue, Shoulder weakness, Weak diaphragm, Increased transaminases)

      HPOsFreeText: Decline in energy and strength reported with each of her four pregnancies most prominent after her youngest daughter's diagnosis of IOPD, Subsequent enzyme assay indicated deficient GAA activity via a dried blood spot (2.2 pmol/punch/hr, control >3.88 pmol/punch/hr), Pulmonary functioning tests (PFTs) showed a decrease in forced vital capacity (FVC) from 93% predicted seated to 72% predicted supine, Laboratory results demonstrated an elevated CK level of 490 U/L (control 30–220 U/L) and mild elevation of transaminases with AST of 83 U/L (control 15–41 U/L) and ALT of 60 U/L (control 14–54 U/L)

      CaseAddInfo: Mother of proband F3P1, found to have minimally symptomatic LOPD

    1. 4-year-old Japanese girl

      Case1: Female, 4 years old, Japanese

      DiseaseAssertion: Thrombocytopenia

      FamilyInfo: 4-generation pedigree available

      ParentalGenotype: See Figure 1 A for parents in the pedigree

      CasePresentingHPOs: HP:0004406, HP:0000979

      (Recurrent epistaxis, purpura)

      CaseHPOFreeText: Mild bleeding tendency

      CaseNotHPOs: N/A

      CaseNotHPOsFreeText: N/A

      ProteinExpression: Flow cytometry showed reduced expression levels

      PlateletAggregation: Platelet aggregation induced by ADP and collagen was markedly reduced but agglutination induced by ristocetin was within the normal range.

      CasePreviousTesting: Direct sequencing analysis around T2231 in exon 14 of the ITGB3 gene. Genomic DNA extracted from the affected and unaffected individuals of the pedigree were amplified by PCR and sequenced (See Figure 2)

      Gene: ITGB3

      Variant: NM_000212.2:c.2231T>C (p.Leu744Pro)

      LegacyVariant: p.Leu718Pro

      ClinVar: 50229

      CAiD: CA143712

      gnomAD: N/A

    1. The patient is a Caucasian 43-year old female

      Case1: Female, 43 years old, Caucasian

      DiseaseAssertion: Thrombasthenia

      FamilyInfo: Pedigree found in Fig. 2B

      ParentalGenotype: See Pedigree Fig 2B

      CasePresentingHPOs: HP:0000132 (Menorrhagia)

      CaseHPOFreeText: Severe and frequent mucocutaneous hemorrhages, intra-peritoneal bleeding

      CaseNotHPOs: N/A

      CaseNotHPOsFreeText: N/A

      ProteinExpression: 25% decrease of GPIbα and a reduced mean value of side scatter in the patient’s platelets.

      PlateletAggregation: Platelet aggregation was markedly reduced in response to ADP, epinephrine, collagen, and arachidonic acid but agglutination induced by ristocetin was normal

      CasePreviousTesting: Screening for mutations was carried out by direct sequencing of PCR-amplified overlapping fragments of reversed transcribed αIIb and β3 mRNA.

      Gene: ITGB3

      Variant: NM_000212.2:c.2231T>C (p.Leu744Pro)

      LegacyVariant: (p.Leu718Pro)

      ClinVar: 50229

      CAiD: CA143712

      gnomAD: N/A

    1. Case#: Downes_2019_BSS, male, age unknown, South-Asian ancestry reported

      DiseaseAssertion: BSS

      FamilyInfo: NR

      ParentalGenotype: NR

      CasePresentingHPOs: NR

      PlateletAggregation: NR

      CaseHPOFreeText: NR

      CaseNotHPOs:

      CaseNotHPOFreeText:

      ProteinExpression: NR

      CasePreviousTesting:

      GenotypingMethod: HTS panel described in supplementary table 3

      PreviouslyPublished:

      Gene: ITGA2B

      Variant: homozygous c.1005_1013del (p.His335_Leu338delinsGln)

      HGVS: NM_000419.5(ITGA2B):c.1005_1013del

      ClinVarID: 626948

      CAID:

      gnomAD: not found in v.2.1.1

      MultipleGeneVariants: