A homozygous missense mutation (P3527S) in the ryanodine receptor type 1 gene on chromosome 19q13 is associated with a recessive form of central core disease (maximum LOD score 5.19).
Observational
Identified a novel homozygous missense mutation in the ryanodine receptor type 1 gene associated with a recessive form of central core disease transiently presenting as multi-minicore disease.
Effect estimate: LOD score 5.19
Abstract Multi‐minicore disease is an autosomal recessive congenital myopathy characterized by the presence of multiple, short‐length core lesions (minicores) in both muscle fiber types. These lesions being nonspecific and the clinical phenotype being heterogeneous, multi‐minicore disease boundaries remain unclear. To identify its genetic basis, we performed a genome‐wide screening in a consanguineous Algerian family in which three children presented in infancy with moderate weakness predominant in axial muscles, pelvic girdle and hands, joint hyperlaxity (hand involvement phenotype), and multiple minicores. We mapped the disease to chromosome 19q13 in this family and, subsequently, in three additional families showing a similar phenotype, with a maximum LOD score of 5.19 for D19S570. This locus was excluded in 16 other multi‐minicore disease families with predominantly axial weakness, scoliosis, and respiratory insufficiency (“classical” phenotype). In the Algerian family, we identified a novel homozygous missense mutation (P3527S) in the ryanodine receptor type 1 gene, a positional candidate gene responsible for the autosomal dominant congenital myopathy central core disease. New muscle biopsies from the three patients at adulthood demonstrated typical central core disease with rods; no cores were found in the healthy parents. This subgroup of families linked to 19q13 represents the first variant of central core disease with genetically proven recessive inheritance and transient presentation as multi‐minicore disease.
Ferreiro et al. (Tue,) conducted a observational in Multi-minicore disease / Central core disease. Homozygous missense mutation (P3527S) in the ryanodine receptor type 1 gene vs. Healthy parents / families with classical phenotype was evaluated on Genetic mapping and mutation identification (LOD score 5.19). A homozygous missense mutation (P3527S) in the ryanodine receptor type 1 gene on chromosome 19q13 is associated with a recessive form of central core disease (maximum LOD score 5.19).