P.5.9 Clinical and molecular analysis of a large cohort of patients with anoctaminopathy

Recessive mutations in the ANO5 gene cause a spectrum of phenotypes ranging from isolated hyperCKaemia to limb girdle muscular dystrophy (LGMD2L), characterized by adult onset proximal lower limb muscular weakness and raised CK values. The recurrent exon 5 mutation (c.191dupA) has been found in most of the British and German patients so far reported. We performed molecular analysis of the ANO5 gene in a large cohort of undiagnosed patients with clinical suspicion of anoctaminopathy. We identified two pathogenic mutations in 42/205 unrelated patients (21%), while a single change only was found in further 14 patients. Fifteen pathogenic changes were novel. The founder c.191dupA mutation represents 61% of mutated alleles but is confirmed to be less prevalent in non-Northern European populations. Retrospective clinical analysis of patients with 2 mutations corroborates previous finding such as the male predominance and absence of major cardiac or respiratory involvement, as well as very mild late onset cases of both sexes and isolated hyperCKaemia only. Our results also confirm anoctaminopathy as one of the most common adult muscular dystrophies in Northern Europe, with a prevalence of about 20–25% in undiagnosed patients. Recessive mutations in the ANO5 gene cause a spectrum of phenotypes ranging from isolated hyperCKaemia to limb girdle muscular dystrophy (LGMD2L), characterized by adult onset proximal lower limb muscular weakness and raised CK values. The recurrent exon 5 mutation (c.191dupA) has been found in most of the British and German patients so far reported. We performed molecular analysis of the ANO5 gene in a large cohort of undiagnosed patients with clinical suspicion of anoctaminopathy. We identified two pathogenic mutations in 42/205 unrelated patients (21%), while a single change only was found in further 14 patients. Fifteen pathogenic changes were novel. The founder c.191dupA mutation represents 61% of mutated alleles but is confirmed to be less prevalent in non-Northern European populations. Retrospective clinical analysis of patients with 2 mutations corroborates previous finding such as the male predominance and absence of major cardiac or respiratory involvement, as well as very mild late onset cases of both sexes and isolated hyperCKaemia only. Our results also confirm anoctaminopathy as one of the most common adult muscular dystrophies in Northern Europe, with a prevalence of about 20–25% in undiagnosed patients.