Two autosomal recessive neuromuscular disorders - FRDA and LGMD2A, in a single Bulgarian pedigree

Abstract

Here we report a single pedigree affected by two different recessive neuromuscular disorders, namely Friedreich ataxia (FRDA) and Limb-Girdle Muscular Dystrophy Type 2A. The molecular genetic testing showed that in this family FRDA is caused by an expanded GAA repeat in compound heterozygous state with a novel point mutation c.442C>T, p.Gln148* on the second allele of the FXN gene. This case of two siblings (male and female) is the first report of Bulgarian FRDA case carrying a point mutation in the FXN gene. The LGMD2A affected individual was found to be compound heterozygous for the two most common CAPN3 mutations for the Bulgarian population (c.550delA, p.Thr184Argfs; c.967G>T, p.Glu323*). To the best of our knowledge we are reporting the first Bulgarian family with two neurological disorders caused by mutations in genes on different chromosomes and segregating independently in the family. This single pedigree with four different mutations is an example for the high genetic heterogeneity of the Bulgarian population.