Eight new mutations and the expanding phenotype variability in muscular dystrophy caused by ANO5

Abstract

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.

A novel missense mutation in ANO5/TMEM16E is causative for gnathodiaphyseal dyplasia in a large Italian pedigree

“…[21][22][23][24] Nineteen different mutations have been identified in homozygosity or compound heterozygosity. Such mutations include six variants causing a frameshift and premature truncation of the protein, 10 missense mutations, 1 splice site mutation causing an in-frame deletion of 24 residues and 2 mutations in hypothetical splice sites whose effects have not been verified at the cDNA level ( Table 2).…”

“…Elevated CK also occurs in subjects with ANO5 recessive mutations including LGMD2L and MMD3 patients, as well as in asymptomatic carriers. [23][24][25] Interestingly, MMD3 patient fibroblasts have defective membrane repair following cell wounding, suggesting that ANO5 may have a physiological role in this process. 27 Defective repair of the sarcolemma following contraction-induced mechanical stress may account for elevated serum CK levels in ANO5-related muscular dystrophy patients.…”

Limb-girdle Muscular Dystrophies

“…223,224 Although highly expressed in skeletal muscle, cardiac myocytes, and bone, its function is still poorly understood. 219,221,222,225 221,224 The most common mutation is a truncating mutation in exon 5, but compound heterozygous missense mutations have also been reported.…”

Borderlines between Sarcopenia and Mild Late-Onset Muscle Disease

“…In recessive LGMD diseases, the severity of the symptoms varies significantly. For example, LGMD2L disease caused by ANO5 gene mutations can be very mild or even asymptomatic, especially in female patients (Penttilä et al, 2012). Of the patients examined in that study, one male patient’s symptoms started at age 70, and at first, they were considered to be a consequence of statin use.…”

“…Of the patients examined in that study, one male patient’s symptoms started at age 70, and at first, they were considered to be a consequence of statin use. He had, however, proximal weakness in the lower limb on examination and dystrophic changes on muscle MRI (Penttilä et al, 2012). Another male patient with a very mild LGMD2L disease is now 78 years old and still walking long distances without aid.…”