P1.26 Occurrence of ANO5 mutation R758C in patients with a muscular dystrophy of unknown etiology

Abstract

Recessive ANO5 gene mutations were recently reported to be the cause of limb-girdle muscular dystrophy type 2L (LGMD2L) and distal non-dysferlin Miyoshi-like myopathy. One of these mutations, c.2272C > T that leads to an amino acid substitution R758C, was found in two Finnish brothers with Miyoshi-like myopathy. R758C mutation was detected in two out of 578 Finnish control chromosomes which gives this mutation a frequency of 0.35% in Finnish population. With such frequency there should be some 50 R758C homozygote patients in Finland on a population of 5 million people. We screened 45 patients with a distal calf myopathy of unknown etiology and/or CK level over 3000. Four of these patients had ancestral origins in Germany and the rest were of Finnish origin. We identified three Finnish patients homozygous and two Finnish and three American patients heterozygous for R758C. In addition, one Finnish patient was a compound heterozygote with R758C in one chromosome and a previously unknown mutation c.2311_2312delCA in the other. R758C homozygote patients had both Miyoshi-like phenotypes and limb-girdle phenotypes as with LGMD2L. Our results indicate that R758C is a frequent cause of muscular dystrophy in Finland. Besides R758C there are at least two other ANO5 mutations in Finland, one of which is the new mutation c.2311_2312delCA. Moreover, R758C occurs also in other European populations.