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.
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 calfhypertrophy 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: Danielle A Griffin; Ryan W Johnson; Jarred M Whitlock; Eric R Pozsgai; Kristin N Heller; William E Grose; W David Arnold; Zarife Sahenk; H Criss Hartzell; Louise R Rodino-Klapac Journal: Hum Mol Genet Date: 2016-02-23 Impact factor: 6.150
Authors: Caterina Marconi; Paolo Brunamonti Binello; Giovanni Badiali; Emanuela Caci; Roberto Cusano; Joseph Garibaldi; Tommaso Pippucci; Alberto Merlini; Claudio Marchetti; Kerry J Rhoden; Luis J V Galietta; Faustina Lalatta; Paolo Balbi; Marco Seri Journal: Eur J Hum Genet Date: 2012-10-10 Impact factor: 4.246
Authors: Gavin Charlesworth; Vincent Plagnol; Kira M Holmström; Jose Bras; Una-Marie Sheerin; Elisavet Preza; Ignacio Rubio-Agusti; Mina Ryten; Susanne A Schneider; Maria Stamelou; Daniah Trabzuni; Andrey Y Abramov; Kailash P Bhatia; Nicholas W Wood Journal: Am J Hum Genet Date: 2012-11-29 Impact factor: 11.025
Authors: Dimitra G Georganopoulou; Vasilis G Moisiadis; Firhan A Malik; Ali Mohajer; Tanya M Dashevsky; Shirley T Wuu; Chih-Kao Hu Journal: Protein J Date: 2021-06-10 Impact factor: 2.371