Novel SGCG mutation causing Limb Girdle Muscular Dystrophy in a Bedouin kindred Gombosh M¹, Halperin D¹, Yogev Y¹, Birk OS^1,2

Consanguineous Bedouin kindred from the Negev region of Israel presented with a phenotype of proximal muscle weakness, affecting several generations in an apparent autosomal recessive mode of inheritance. Linkage analysis was performed using 750K SNP arrays, yielding a single disease-associated locus with a LOD score of 2.93. Whole-exome sequencing data of an affected individual were analyzed and filtered using our in-house databases along with open access databases. Variants within the locus were further analyzed using Sanger sequencing and restriction analysis. Of those variants, only a single homozygous c.703-1G>A splice-site mutation in SGCG showed full segregation within the family and was not found in 400 healthy Bedouin controls. In-silico analysis of the novel c.703-1G>A variant showed that it is likely to abolish a splice acceptor site in the final exon, yielding a truncated protein, or leading to nonsense mediated decay. Mutations in SGCG were previously described as causative for Duchene-like Limb Girdle Muscular Dystrophy (LGMD) type 2C. Our data suggest that the novel SGCG homozygous mutation is the cause for the dominantly inherited disease in this kindred.