Family 4 - Patients 4a and 4b

FamilyPresentingHPOs: HP:0007340, HP:0003701, HP:0000467, HP:0003327, HP:0010628, HP:0002015, HP:0003306, HP:0002111, HP:0011807, HP:0003554, HP:0002111, HP:0100298, HP:0040081

HPOsFreeText: myopathic muscle unit action potentials, 4b muscular pathology with mild atrophy of type 1 and 2 fibers with many moth‐eaten fibers, no vacuoles, no glycogen excess

FamilyNotHPOs: HP:0003691, HP:0002650

NotHPOsFreeText:

Ethnicity: Iranian

ProbandLabel: 4a, female, 7yo at onset, 30yo at diagnosis

FamilyAddInfo: 4b (male) dx at 23yo, 4a MRC sum score = 84, 4b MRC sum score = 86, both patients required use of NIV

FamilyPreviousTesting: Respiratory Evaluation: 4a FVC = 29%, 4b FVC = 66%, 4a CK = 760 U/L, 4b CK = 3,257 U/L, muscle pathology (examined only in 4b), DBS enzyme activity (with inhibition) for 4a = 0.1 μmol/L/h, for 4b = 0.13 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

VariantAllele1: 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

VariantAllele2: NM_000152.3:c.1650delG

Clinvar: n/a

CAID: CA627699787, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA627699787

gnomAD: n/a

Patient1: Male, 26 years report, Iranian, Iran

CasePresentingHPOs: HP:0002098, HP:0001324, HP:0003236, HP:0002910 (Respiratory distress, Muscle weakness, Increased serum CK, Increased transaminases)

HPOsFreeText: GAA measurement from dried blood specimen at pH 3.8 was 0.19 nmol/spot * 21 h (ref 0.9-7.2) with acarbose and 0.89 nmol/spot * 21 h (ref 1.5-10) without acarbose and 4.40 nmol/spot * 21 h at pH 7.0 (ref 1.8-17.1), AST levels at 211 (ref 0-45), ALT levels at 294 (ref 5-40), CPK levels at 1925 (ref 25-200), FEV1 at 0.81, FEV1/FVC at 89.25

CaseAddInfo: Sibling of P2, Unsure of which second variant patient has since it is never specified

Patient2: Female, 34 years report, Iranian, Iran

CasePresentingHPOs: HP:0002098, HP:0003236, HP:0002910 (Respiratory distress, Increased serum CK, Increased transaminases)

HPOsFreeText: GAA measurement from dried blood specimen at pH 3.8 was 0.13 nmol/spot * 21 h (ref 0.9-7.2) with acarbose and 0.65 nmol/spot * 21 h (ref 1.5-10) without acarbose and 3.84 nmol/spot * 21 h at pH 7.0 (ref 1.8-17.1), AST levels at 165 (ref 0-45), ALT levels at 261 (ref 5-40), CPK levels at 1212 (ref 25-200), FEV1 at 0.83, FEV1/FVC at 90.25

CaseAddInfo: Sibling of P1