From the age of 30 years, the proposita (case III.4 in Fig. 1 a) showed a prevalently distal muscle phenotype characterized by stepping gait with progressive pes cavus, mild proximal muscle weakness in the lower limbs, and scoliosis.
Case III.4: Female, age 30
DiseaseAssertion: Distal myopathy
FamilyInfo: Figure 1, similar distal muscle weakness in four relatives. Patients I.2 and II.2 experienced foot drop while walking. Patient III.2 muscle biopsy findings suggestive of core myopathy suggested a disorder similar to his youngest sister. Patient IV.1 displayed a less progressive muscular phenotype than her older relatives and tested negative for the mutation in RYR1
CasePresentingHPOs: HP:0001761, HP:0008994, HP:0002650
"Pes cavus, Proximal muscle weakness in lower limbs, Scoliosis"
CaseHPOFreeText: stepping gait
CasePreviousTesting: muscle biopsy showed fiber size variability, increased internal nuclei and histochemical evidence of eccentric core-like lesions, Analysis of RYR1 revealed a heterozygous c.880G > A:p.(Glu294Lys) mutation
GenotypingMethod: Amplicon-based Sanger sequencing, MotorPlex used to analyze a large set of genes that cause known forms of non-syndromic muscle disorders
MultipleGeneVariants:
(1) MHY7Variant: Novel
Variant: NM_000257.4:c.4303T>C
ClinVar: not found
CAID: CA389040164
gnomAD: not found
(2) RYR1Variant:
Variant: NM_000540.2:c.880G>A
ClinVar: 590621
CAID: CA072725
gnomAD: https://gnomad.broadinstitute.org/variant/19-38939074-G-A?dataset=gnomad_r2_1
Total allele frequency: 0.00006159 European (non-Finnish)