title: Eight new mutations and the expanding phenotype variability in muscular dystrophy caused by ANO5.
abstract: OBJECTIVE
  Description of 8 new ANO5 mutations and significant expansion of the clinical phenotype spectrum associated with previously known and unknown mutations to improve diagnostic accuracy.
  
  
  METHODS
  DNA samples of 101 patients in 95 kindreds at our quaternary referral center in Finland, who had undetermined limb-girdle muscular dystrophy (LGMD), calf distal myopathy, or creatine kinase (CK) elevations of more than 2,000 IU/L, were selected for ANO5 genetic evaluation, and the clinical findings of patients with mutations were retrospectively analyzed.
  
  
  RESULTS
  A total of 25 patients with muscular dystrophy caused by 11 different recessive mutations in the ANO5 gene were identified. The vast majority of mutations, 8 of 11, proved to be previously unknown new mutations. The most frequent mutation, c.2272C>T (p.R758C), was present in 20 patients. The phenotypes associated with this and the common European mutation, c.191dupA, varied from nearly asymptomatic high hyperCKemia to severe LGMD with consistently milder phenotypes in female patients.
  
  
  CONCLUSIONS
  Mutations in ANO5 are a frequent cause of undetermined muscular dystrophy, with both distal and proximal presentation. Other types include high hyperCKemia, myalgia, or calf hypertrophy over decades without significant weakness, especially in female patients. Mutations are distributed all over the gene, indicating that muscular dystrophy caused by ANO5 can be expected to occur in all populations.
authors.affiliation: Neuromuscular Research Unit, Tampere University and University Hospital, Tampere, Finland. sini.penttila@uta.fi
authors.forename: S
authors.initials: S
authors.lastname: Penttilä
authors.forename: J
authors.initials: J
authors.lastname: Palmio
authors.forename: T
authors.initials: T
authors.lastname: Suominen
authors.forename: O
authors.initials: O
authors.lastname: Raheem
authors.forename: A
authors.initials: A
authors.lastname: Evilä
authors.forename: N
authors.initials: N
authors.lastname: Muelas Gomez
authors.forename: G
authors.initials: G
authors.lastname: Tasca
authors.forename: L B
authors.initials: LB
authors.lastname: Waddell
authors.forename: N F
authors.initials: NF
authors.lastname: Clarke
authors.forename: A
authors.initials: A
authors.lastname: Barboi
authors.forename: P
authors.initials: P
authors.lastname: Hackman
authors.forename: B
authors.initials: B
authors.lastname: Udd
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000075368:Anoctamins; D015153:Blotting, Western; D018118:Chloride Channels / Q000235:genetics*; D015331:Cohort Studies; D003402:Creatine Kinase / Q000097:blood; D004247:DNA / Q000235:genetics; D005260:Female; D005387:Finland; D005808:Genes, Recessive; D005820:Genetic Testing; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000209:etiology; D018482:Muscle, Skeletal / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D009154:Mutation / Q000502:physiology*; D010641:Phenotype; D015203:Reproducibility of Results
chemical_list: C547813:ANO5 protein, human; D000075368:Anoctamins; D018118:Chloride Channels; D004247:DNA; D003402:Creatine Kinase