title: [Muscular dystrophy due to mutations in anoctamin 5: clinical and molecular genetic findings].
abstract: Recessive mutations in the anoctamin 5 (ANO5) gene have been recently identified in families with limb girdle muscular dystrophy (LGMD2L) and distal non-dysferlin Miyoshi myopathy. Anoctamin 5 is supposed to be a putative calcium-activated chloride channel. We report five German patients (four index patients) with muscle dystrophy due to mutations in the ANO5 gene. Sequencing of the ANO5 exons 5, 13 and 20 was performed to screen for a common c.191dupA mutation and two other reported mutations (c.1295C>G and p.R758C). The whole coding region of the ANO5 gene was sequenced to identify new mutations. Phenotypically, three patients showed LGMD and one patient Miyoshi type distal myopathy. One sibling had asymptomatic hyperCKemia. The age at onset was 64, 38 and 40 years in patients with LGMD and 23 years in the patient with distal myopathy. The four symptomatic patients showed remarkable asymmetric muscle involvement. There was marked CK elevation (11 to 30 times). Electron microscopy showed multifocal gaps in the sarcolemmal membrane. All patients harboured the common c.191dupA mutation in at least one allele. Two patients with LGMD were homozygous and the third patient and his asymptomatic sister were compound heterozygous for the c.191dupA mutation and a novel p.T548I mutation. The patient with distal myopathy harboured the p.R758C mutation in the second allele. Mutations in the ANO5 gene seem to be a relatively common cause of muscular dystrophy in Germany. Cases with late onset or asymptomatic hyperCKemia can occur. Clinically, asymmetric manifestation is typical.
authors: Klinik und Poliklinik für Neurologie, Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Str. 40, 06097 Halle (Saale), Deutschland. marcus.deschauer@medizin.uni-halle.de
authors: M
authors: M
authors: Deschauer
authors: P R
authors: PR
authors: Joshi
authors: D
authors: D
authors: Gläser
authors: F
authors: F
authors: Hanisch
authors: G
authors: G
authors: Stoltenburg
authors: S
authors: S
authors: Zierz
mesh_terms: D000328:Adult; D000368:Aged; D000075368:Anoctamins; D018118:Chloride Channels / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009136:Muscular Dystrophies / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: C547813:ANO5 protein, human; D000075368:Anoctamins; D018118:Chloride Channels