title: 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.
abstract: 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 British and German LGMD2L 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-Northern European 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 hyperCKaemia 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 Northern Europe, with a prevalence of about 20%-25% in unselected undiagnosed cases.
authors.affiliation: Institute of Genetic Medicine, International Centre for Life, Newcastle upon Tyne, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Sarkozy
authors.forename: Debbie
authors.initials: D
authors.lastname: Hicks
authors.forename: Judith
authors.initials: J
authors.lastname: Hudson
authors.forename: Steve H
authors.initials: SH
authors.lastname: Laval
authors.forename: Rita
authors.initials: R
authors.lastname: Barresi
authors.forename: David
authors.initials: D
authors.lastname: Hilton-Jones
authors.forename: Marcus
authors.initials: M
authors.lastname: Deschauer
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Harris
authors.forename: Laura
authors.initials: L
authors.lastname: Rufibach
authors.forename: Esther
authors.initials: E
authors.lastname: Hwang
authors.forename: Rumaisa
authors.initials: R
authors.lastname: Bashir
authors.forename: Maggie C
authors.initials: MC
authors.lastname: Walter
authors.forename: Sabine
authors.initials: S
authors.lastname: Krause
authors.forename: Peter
authors.initials: P
authors.lastname: van den Bergh
authors.forename: Isabel
authors.initials: I
authors.lastname: Illa
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pénisson-Besnier
authors.forename: Liesbeth
authors.initials: L
authors.lastname: De Waele
authors.forename: Doug
authors.initials: D
authors.lastname: Turnbull
authors.forename: Michela
authors.initials: M
authors.lastname: Guglieri
authors.forename: Bertold
authors.initials: B
authors.lastname: Schrank
authors.forename: Benedikt
authors.initials: B
authors.lastname: Schoser
authors.forename: Jürgen
authors.initials: J
authors.lastname: Seeger
authors.forename: Herbert
authors.initials: H
authors.lastname: Schreiber
authors.forename: Dieter
authors.initials: D
authors.lastname: Gläser
authors.forename: Michelle
authors.initials: M
authors.lastname: Eagle
authors.forename: Geraldine
authors.initials: G
authors.lastname: Bailey
authors.forename: Richard
authors.initials: R
authors.lastname: Walters
authors.forename: Cheryl
authors.initials: C
authors.lastname: Longman
authors.forename: Fiona
authors.initials: F
authors.lastname: Norwood
authors.forename: John
authors.initials: J
authors.lastname: Winer
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.forename: Michael
authors.initials: M
authors.lastname: Hanna
authors.forename: Mark
authors.initials: M
authors.lastname: Roberts
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Bindoff
authors.forename: Charlotte
authors.initials: C
authors.lastname: Brierley
authors.forename: Robert G
authors.initials: RG
authors.lastname: Cooper
authors.forename: David A
authors.initials: DA
authors.lastname: Cottrell
authors.forename: Nick P
authors.initials: NP
authors.lastname: Davies
authors.forename: Andrew
authors.initials: A
authors.lastname: Gibson
authors.forename: Gráinne S
authors.initials: GS
authors.lastname: Gorman
authors.forename: Simon
authors.initials: S
authors.lastname: Hammans
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Jackson
authors.forename: Aijaz
authors.initials: A
authors.lastname: Khan
authors.forename: Russell
authors.initials: R
authors.lastname: Lane
authors.forename: John
authors.initials: J
authors.lastname: McConville
authors.forename: Meriel
authors.initials: M
authors.lastname: McEntagart
authors.forename: Ali
authors.initials: A
authors.lastname: Al-Memar
authors.forename: John
authors.initials: J
authors.lastname: Nixon
authors.forename: Jay
authors.initials: J
authors.lastname: Panicker
authors.forename: Matt
authors.initials: M
authors.lastname: Parton
authors.forename: Richard
authors.initials: R
authors.lastname: Petty
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Price
authors.forename: Wojtek
authors.initials: W
authors.lastname: Rakowicz
authors.forename: Partha
authors.initials: P
authors.lastname: Ray
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Schapira
authors.forename: Robert
authors.initials: R
authors.lastname: Swingler
authors.forename: Chris
authors.initials: C
authors.lastname: Turner
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Wagner
authors.forename: Paul
authors.initials: P
authors.lastname: Maddison
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Shaw
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
mesh_terms: D000328:Adult; D000368:Aged; D000075368:Anoctamins; D018118:Chloride Channels / Q000235:genetics* / Q000378:metabolism; D005060:Europe / Q000453:epidemiology; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D049288:Muscular Dystrophies, Limb-Girdle / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D015995:Prevalence; D012189:Retrospective Studies; D012737:Sex Factors
chemical_list: C547813:ANO5 protein, human; D000075368:Anoctamins; D018118:Chloride Channels
keywords: ANO5; LGMD2L; gender; muscular dystrophy