12
Patient12: Male, 19 years report, 13 years onset
CasePresentingHPOs: HP:0001324 (Muscle weakness)
HPOsFreeText: GAA activity 9.9% from leukocyte
CaseNotHPOs: HP:0002098, HP:0002240, HP:0001640 (Respiratory distress, Hepatomegaly, Cardiomegaly)
NotHPOsFreeText: No wheelchair needed, Respiratory Assistance not needed
CaseAddInfo: LOPD
CaseOPOPD-6: Female, Taiwan, Birth diagnosis
HPOsFreeText: GAA (MS/MS) enzyme activity at 0.75 umol/hr/L
GenotypingMethod: GAA Gene Sequencing and PCR Amplification
Variant1: NM_000152.4:c.569G>A (p.Arg190His)
ClinVar: 188809 https://www.ncbi.nlm.nih.gov/clinvar/variation/188809/
gnomAD: African 6.166e-5, Overall 1.602e-5 http://gnomad.broadinstitute.org/variant/17-78079570-G-A
Variant2: 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
CaseAddInfo: One Pompe Mutation and One Pseudodeficency Mutation, 2 others have the same genotype
35
Patient35: male, Caucasian
CasePresentingHPOs: HP:0003676, HP:0003236, HP:0003325, HP:0008994, HP:0003458, HP:0003560, HP:0030121
HPOsFreeText: CK < 10x increase, difficulty ascending stairs, inability to stand without aid, treated with ERT
CaseNotHPOs: HP:0002093
CaseAddInfo: onset as young adult. Older sister also affected with onset at 21 yo. She now exhibits scoliosis, fatigability, paraspinal muscle atrophy, proximal upper limp atrophy, and weakness. Calpain deficiency detected via immunoblot could be connected to CAPN3 variants (p.Gly333Asp [c.998G > A] and p.Ala726Ser [c.2176G > T]).
CasePreviousTesting: same as group, EMG, muscle biopsy, immunoblot analysis
CaseGenotypingMethod: same as group
Variant1: NM_000152.4(GAA):c.569G>A (p.Arg190His)
ClinVar: 188809, https://www.ncbi.nlm.nih.gov/clinvar/variation/188809/
gnomAD: 8.276e-06, http://exac.broadinstitute.org/variant/17-78079570-G-A
Variant2: NM_000152.3:c.2020C>G
CAID: CA401370092, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA401370092
gnomAD: n/a