Family 6 - Patients 6a and 6b

FamilyPresentingHPOs: HP:0007340, HP:0003701, HP:0000467, HP:0003327, HP:0200136, HP:0003691, HP:0003306, HP:0002650, HP:0040081, HP:0002111, HP:0100284

HPOsFreeText: myopathic muscle unit action potentials, 6a muscle pathology with vacuolar myopathy with glycogen excess

FamilyNotHPOs: HP:0010628

Ethnicity: Iranian

ProbandLabel: 6a, male, 12yo at onset, 25yo at diagnosis

FamilyAddInfo: 6b (male) dx at 33yo, 6a MRC sum score = 78, 6b MRC sum score = 79, both patients required use of NIV

FamilyPreviousTesting: Respiratory Evaluation: 6a FVC = 19%, 6b FVC = 38%, 6a CK = 820 U/L, 6b CK = 503 U/L, muscle pathology (examined only in 6a), DBS enzyme activity (with inhibition) for 6a = 0 μmol/L/h, for 6b = 0.21 μmol/L/h, NCS, EMG

FamilyGenotypingMethod: GAA analyzed with Sanger Sequencing for entire coding region and conserved exon-intron splice junctions, PCR performed for deletion screening

Variant: NM_000152.4(GAA):c.1979G>A (p.Arg660His)

ClinVar: 189172, https://www.ncbi.nlm.nih.gov/clinvar/variation/189172/

gnomAD: 3.279e-05, http://exac.broadinstitute.org/variant/17-78086765-G-A

Case47

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.655G>A (p.Gly219Arg)

ClinVar: 189065 https://www.ncbi.nlm.nih.gov/clinvar/variation/189065/

gnomAD: African 4.024e-5, Overall 1.809e-5 http://gnomad.broadinstitute.org/variant/17-78079656-G-A

Variant2: NM_000152.4:c.1979G>A (p.Arg660His)

ClinVar: 189172 https://www.ncbi.nlm.nih.gov/clinvar/variation/189172/

gnomAD: African 2.546e-4, Overall 3.680e-5 http://gnomad.broadinstitute.org/variant/17-78086765-G-A

CaseAddInfo: Infantile Onset Pompe Disease