ClinVar

Jungbluth et al. (2002) identified a recessive RYR1 mutation as a cause of central core disease (117000). They reported 3 patients from 2 consanguineous families with symptoms of congenital myopathy, cores on muscle biopsy, and confirmed linkage to the RYR1 locus. Molecular genetic studies in 1 family identified a homozygous 14545G-A change in exon 101 of the RYR1 gene, resulting in a val4849-to-ile (V4849I) substitution. Skeletal muscle biopsy of the patient with the homozygous V4849I mutation showed minicores.

Kossugue et al. (2007) identified a homozygous V4849I substitution in a 9-year-old girl with autosomal recessive central core disease. She was born of unaffected consanguineous parents. Skeletal muscle biopsy showed type 1 fiber predominance,and several diffuse large and minicores within the fibers.

Monnier et al. (2008) reported a 9-year-old Dutch boy with a severe autosomal recessive myopathy with ptosis and facial diplegia (255320) associated with compound heterozygous RYR1 mutations, V4849I and a 4-bp insertion (180901.0032). The patient had severe neonatal hypotonia, delayed motor development, amyotrophy, kyphoscoliosis, required ventilatory assistance at age 4 years, and was never able to walk. A sister had died at age 5 years of myopathic respiratory insufficiency. Monnier et al. (2008) postulated that since the patient had a hypomorphic frameshift RYR1 allele, the resultant phenotype was more severe compared to those patients with homozygous V4849I mutations.