title: Frequency and characterisation of anoctamin 5 mutations in a cohort of Italian limb-girdle muscular dystrophy patients.
abstract: Limb-girdle muscular dystrophy (LGMD) 2L, caused by mutations in the anoctamin 5 (ANO5) gene, is the third most common LGMD in Northern and Central Europe, where the c.191dupA mutation causes the majority of cases. We evaluated data from 228 Italian LGMD patients to determine the prevalence of LGMD2L and the c.191dupA mutation, and to describe the clinical, muscle biopsy, and magnetic resonance imaging findings in these patients. Forty-three patients who lacked molecular diagnosis were studied for ANO5 mutations, and four novel mutations were found in three probands. Only one proband carried the c.191dupA mutation, which was compound heterozygous with c.2516T>G. Two probands were homozygous for the c.1627dupA and c.397A>T mutations, respectively, while a fourth proband had a compound heterozygous status (c.220C>T and c.1609T>C). Therefore occurrence and molecular epidemiology of LGMD2L in this Italian cohort differed from those observed in other European countries. ANO5 mutations accounted for ∼2% of our sample. Affected patients exhibited benign progression with variable onset and an absence of cardiac and respiratory impairment; muscle biopsy generally showed mild signs, except when performed on the quadriceps muscles; MRI showed predominant involvement of the posterior thigh. Overall these common clinical, morphological and imaging findings could be useful in differential diagnosis.
authors: Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors: Francesca
authors: F
authors: Magri
authors: Roberto
authors: R
authors: Del Bo
authors: Maria Grazia
authors: MG
authors: D'Angelo
authors: Monica
authors: M
authors: Sciacco
authors: Sandra
authors: S
authors: Gandossini
authors: Alessandra
authors: A
authors: Govoni
authors: Laura
authors: L
authors: Napoli
authors: Patrizia
authors: P
authors: Ciscato
authors: Francesco
authors: F
authors: Fortunato
authors: Erika
authors: E
authors: Brighina
authors: Sara
authors: S
authors: Bonato
authors: Andreina
authors: A
authors: Bordoni
authors: Valeria
authors: V
authors: Lucchini
authors: Stefania
authors: S
authors: Corti
authors: Maurizio
authors: M
authors: Moggio
authors: Nereo
authors: N
authors: Bresolin
authors: Giacomo Pietro
authors: GP
authors: Comi
mesh_terms: D000328:Adult; D000075368:Anoctamins; D018118:Chloride Channels / Q000235:genetics*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007558:Italy; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000209:etiology; D049288:Muscular Dystrophies, Limb-Girdle / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree
chemical_list: C547813:ANO5 protein, human; D000075368:Anoctamins; D018118:Chloride Channels