Migration of an ancestral dysferlin splicing mutation from the Iberian peninsula to South America

Miyoshi myopathy, LGMD2B and DMAT are primary dysferlinopathies that belong to a group of muscular dystrophies inherited in an autosomal recessive mode. Additional presentations range from isolated hyperCKemia to severe functional disability. LGMD2B involves predominantly the proximal muscles of the lower limbs whereas in Miyoshi myopathy the muscles involved are those of the posterior muscle compartment of the calf. DMAT is characterized by anterior tibial muscle weakness which rapidly progresses to the lower and upper proximal muscles. Onset is usually in young adults, but congenital and late-onset forms have also been reported. We present the first Uruguayan patient to have been diagnosed with Miyoshi myopathy and four Portuguese patients that carry a novel mutation in exon12/intron12 boundary: c.1180_1180 + 7delAGTGCGTG (r.1054_1284del) in the DYSF gene. Evidence of a founder effect due to a common ancestral origin of this mutation was detected in heterozygosity in four patients and in homozygosity in one patient. The homozygous patient has no proven inbreeding so it can be inferred that the mutation is identical by descent. All patients shared a common haplotypes block identical in state between markers Cy172-H32 and D2S211. We believe that it derives from a common mutational event which is ancestral because of the recombination between the mutated gene and the telomeric flanking marker D2S2113. As this haplotype is not common among the Portuguese population, it is very unlikely that these mutated DYSF alleles represent recurrent events. This is the sixth founder effect of the DYSF gene to be found in the world so far.