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ANO5 Gene Analysis in a Large Cohort of Patients with Anoctaminopathy: Confirmation of Male Prevalence and High Occurrence of the Common Exon 5 Gene Mutation
Author(s) -
Sarkozy Anna,
Hicks Debbie,
Hudson Judith,
Laval Steve H.,
Barresi Rita,
HiltonJones David,
Deschauer Marcus,
Harris Elizabeth,
Rufibach Laura,
Hwang Esther,
Bashir Rumaisa,
Walter Maggie C.,
Krause Sabine,
Bergh Peter,
Illa Isabel,
PénissonBesnier Isabelle,
Waele Liesbeth,
Turnbull Doug,
Guglieri Michela,
Schrank Bertold,
Schoser Benedikt,
Seeger Jürgen,
Schreiber Herbert,
Gläser Dieter,
Eagle Michelle,
Bailey Geraldine,
Walters Richard,
Longman Cheryl,
Norwood Fiona,
Winer John,
Muntoni Francesco,
Hanna Michael,
Roberts Mark,
Bindoff Laurence A.,
Brierley Charlotte,
Cooper Robert G.,
Cottrell David A.,
Davies Nick P.,
Gibson Andrew,
Gorman Gráinne S.,
Hammans Simon,
Jackson Andrew P.,
Khan Aijaz,
Lane Russell,
McConville John,
McEntagart Meriel,
AlMemar Ali,
Nixon John,
Panicker Jay,
Parton Matt,
Petty Richard,
Price Christopher J.,
Rakowicz Wojtek,
Ray Partha,
Schapira Anthony H.,
Swingler Robert,
Turner Chris,
Wagner Kathryn R.,
Maddison Paul,
Shaw Pamela J.,
Straub Volker,
Bushby Kate,
Lochmüller Hanns
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22342
Subject(s) - biology , exon , genetics , compound heterozygosity , muscular dystrophy , limb girdle muscular dystrophy , mutation , phenotype , age of onset , gene , allele , weakness , disease , medicine , anatomy
Limb girdle muscular dystrophy type 2L or anoctaminopathy is a condition mainly characterized by adult onset proximal lower limb muscular weakness and raised CK values, due to recessive ANO5 gene mutations. An exon 5 founder mutation (c.191dupA) has been identified in most of the B ritish and G erman LGMD 2 L patients so far reported. We aimed to further investigate the prevalence and spectrum of ANO5 gene mutations and related clinical phenotypes, by screening 205 undiagnosed patients referred to our molecular service with a clinical suspicion of anoctaminopathy. A total of 42 unrelated patients had two ANO5 mutations (21%), whereas 14 carried a single change. We identified 34 pathogenic changes, 15 of which are novel. The c.191dupA mutation represents 61% of mutated alleles and appears to be less prevalent in non‐ N orthern E uropean populations. Retrospective clinical analysis corroborates the prevalently proximal lower limb phenotype, the male predominance and absence of major cardiac or respiratory involvement. Identification of cases with isolated hyper CK aemia and very late symptomatic male and female subjects confirms the extension of the phenotypic spectrum of the disease. Anoctaminopathy appears to be one of the most common adult muscular dystrophies in N orthern E urope, with a prevalence of about 20%–25% in unselected undiagnosed cases.