Dysferlinopathy in the Jews of the Caucasus: A frequent mutation in the dysferlin gene

Abstract

Dysferlin encoding gene (DYS) is mutated in the autosomal recessive disorders Miyoshi myopathy, Limb Girdle Muscular Dystrophy type 2B (LGMD2B) and distal anterior compartment myopathy, causing dysferlin deficiency in muscle biopsy. Three ethnic clusters have previously been described in Dysferlinopathy: the Libyan Jewish population originating in the area of Tripoli, Italian and Spanish populations. We report another cluster of this muscular dystrophy in Israel among Jews of the Caucasus region. A genomic analysis of the dysferlin coding sequence performed in patients from this ethnic group, who demonstrated an absence of dysferlin expression in muscle biopsy, revealed a homozygous frameshift mutation of G deletion at codon 927 (2779delG) predicting a truncated protein and a complete loss of functional protein. The possible existence of a founder effect is strengthened by our finding of a 4% carrier frequency in this community. These findings are important for genetic counseling and also enable a molecular diagnosis of LGMD2B in Jews of the Caucasus region.