| Identified Mutation |
Arg4861His; Among 7 of 25 unrelated individuals with congenital myopathy-1A (CMYP1A; 117000) with central cores on muscle biopsy, Tilgen et al. (2001) identified a heterozygous c.14582G-A transition in the RYR1 gene, resulting in an arg4861-to-his (R4861H) substitution at a highly conserved residue in the C-terminal region of the protein.
In affected members of 2 unrelated families (CCD07 and CCD15) and an unrelated patient (CCD09) with CMYP1A, Monnier et al. (2001) identified a heterozygous R4861H mutation in exon 101 of the RYR1 gene. The mutation occurred de novo in patient CCD09.
Quinlivan et al. (2003) identified a de novo heterozygous R4861H mutation in exon 101 of the RYR1 gene in an 11-year-old boy (family D) with CMYP1A. Functional studies of the variant were not performed. As an infant, he had hypotonia with poor feeding. He later showed delayed motor development, inability to walk independently, congenital hip dislocation, lordosis, and upper limb involvement.
Sato et al. (2008) identified heterozygosity for the R4861H mutation in a 6-month-old Japanese boy (patient 2) with CMYP1A manifest as 'congenital neuromuscular disease with uniform type 1 fiber' (CNMDU1). He had poor sucking, muscle weakness, joint contractures, and 99.9% type 1 muscle fibers on skeletal muscle biopsy |