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

Anna Sarkozy, Debbie Hicks, Judith Hudson, Steve H. Laval, Rita Barresi, David Hilton-Jones, Marcus Deschauer, Elizabeth Harris, Laura Rufibach, Esther Hwang, Rumaisa Bashir, Maggie C. Walter, Sabine Krause, Peter van den Bergh, Isabel Illa, Isabelle Penisson-Besnier, Liesbeth De Waele, Doug Turnbull, Michela Guglieri, Bertold Schrank & 43 others Benedikt Schoser, Jurgen Seeger, Herbert Schreiber, Dieter Glaeser, Michelle Eagle, Geraldine Bailey, Richard Walters, Cheryl Longman, Fiona Norwood, John Winer, Francesco Muntoni, Michael Hanna, Mark Roberts, Laurence A. Bindoff, Charlotte Brierley, Robert G. Cooper, David A. Cottrell, Nick P. Davies, Andrew Gibson, Grainne S. Gorman, Simon Hammans, Andrew P. Jackson, Aijaz Khan, Russell Lane, John McConville, Meriel McEntagart, Ali Al-Memar, John Nixon, Jay Panicker, Matt Parton, Richard Petty, Christopher J. Price, Wojtek Rakowicz, Partha Ray, Anthony H. Schapira, Robert Swingler, Chris Turner, Kathryn R. Wagner, Paul Maddison, Pamela J. Shaw, Volker Straub, Kate Bushby, Hanns Lochmuller

    Research output: Contribution to journalArticle

    30 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)1111-1118
    Number of pages8
    JournalHuman Mutation
    Volume34
    Issue number8
    DOIs
    Publication statusPublished - 2013

    Keywords

    • PHENOTYPE
    • LGMD2L
    • 2L
    • GIRDLE MUSCULAR-DYSTROPHY
    • muscular dystrophy
    • gender
    • ANO5
    • MYOPATHY

    Cite this

    Sarkozy, Anna ; Hicks, Debbie ; Hudson, Judith ; Laval, Steve H. ; Barresi, Rita ; Hilton-Jones, David ; Deschauer, Marcus ; Harris, Elizabeth ; Rufibach, Laura ; Hwang, Esther ; Bashir, Rumaisa ; Walter, Maggie C. ; Krause, Sabine ; van den Bergh, Peter ; Illa, Isabel ; Penisson-Besnier, Isabelle ; De Waele, Liesbeth ; Turnbull, Doug ; Guglieri, Michela ; Schrank, Bertold ; Schoser, Benedikt ; Seeger, Jurgen ; Schreiber, Herbert ; Glaeser, 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, Grainne S. ; Hammans, Simon ; Jackson, Andrew P. ; Khan, Aijaz ; Lane, Russell ; McConville, John ; McEntagart, Meriel ; Al-Memar, 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 ; Lochmuller, Hanns. / 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. In: Human Mutation. 2013 ; Vol. 34, No. 8. pp. 1111-1118.
    @article{ffd2a0fced1e41809204dc15b9638ca7,
    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.",
    keywords = "PHENOTYPE, LGMD2L, 2L, GIRDLE MUSCULAR-DYSTROPHY, muscular dystrophy, gender, ANO5, MYOPATHY",
    author = "Anna Sarkozy and Debbie Hicks and Judith Hudson and Laval, {Steve H.} and Rita Barresi and David Hilton-Jones and Marcus Deschauer and Elizabeth Harris and Laura Rufibach and Esther Hwang and Rumaisa Bashir and Walter, {Maggie C.} and Sabine Krause and {van den Bergh}, Peter and Isabel Illa and Isabelle Penisson-Besnier and {De Waele}, Liesbeth and Doug Turnbull and Michela Guglieri and Bertold Schrank and Benedikt Schoser and Jurgen Seeger and Herbert Schreiber and Dieter Glaeser and Michelle Eagle and Geraldine Bailey and Richard Walters and Cheryl Longman and Fiona Norwood and John Winer and Francesco Muntoni and Michael Hanna and Mark Roberts and Bindoff, {Laurence A.} and Charlotte Brierley and Cooper, {Robert G.} and Cottrell, {David A.} and Davies, {Nick P.} and Andrew Gibson and Gorman, {Grainne S.} and Simon Hammans and Jackson, {Andrew P.} and Aijaz Khan and Russell Lane and John McConville and Meriel McEntagart and Ali Al-Memar and John Nixon and Jay Panicker and Matt Parton and Richard Petty and Price, {Christopher J.} and Wojtek Rakowicz and Partha Ray and Schapira, {Anthony H.} and Robert Swingler and Chris Turner and Wagner, {Kathryn R.} and Paul Maddison and Shaw, {Pamela J.} and Volker Straub and Kate Bushby and Hanns Lochmuller",
    year = "2013",
    doi = "10.1002/humu.22342",
    language = "English",
    volume = "34",
    pages = "1111--1118",
    journal = "Human Mutation",
    issn = "1059-7794",
    publisher = "Wiley",
    number = "8",

    }

    Sarkozy, A, Hicks, D, Hudson, J, Laval, SH, Barresi, R, Hilton-Jones, D, Deschauer, M, Harris, E, Rufibach, L, Hwang, E, Bashir, R, Walter, MC, Krause, S, van den Bergh, P, Illa, I, Penisson-Besnier, I, De Waele, L, Turnbull, D, Guglieri, M, Schrank, B, Schoser, B, Seeger, J, Schreiber, H, Glaeser, D, Eagle, M, Bailey, G, Walters, R, Longman, C, Norwood, F, Winer, J, Muntoni, F, Hanna, M, Roberts, M, Bindoff, LA, Brierley, C, Cooper, RG, Cottrell, DA, Davies, NP, Gibson, A, Gorman, GS, Hammans, S, Jackson, AP, Khan, A, Lane, R, McConville, J, McEntagart, M, Al-Memar, A, Nixon, J, Panicker, J, Parton, M, Petty, R, Price, CJ, Rakowicz, W, Ray, P, Schapira, AH, Swingler, R, Turner, C, Wagner, KR, Maddison, P, Shaw, PJ, Straub, V, Bushby, K & Lochmuller, H 2013, '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', Human Mutation, vol. 34, no. 8, pp. 1111-1118. https://doi.org/10.1002/humu.22342

    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. / Sarkozy, Anna; Hicks, Debbie; Hudson, Judith; Laval, Steve H.; Barresi, Rita; Hilton-Jones, David; Deschauer, Marcus; Harris, Elizabeth; Rufibach, Laura; Hwang, Esther; Bashir, Rumaisa; Walter, Maggie C.; Krause, Sabine; van den Bergh, Peter; Illa, Isabel; Penisson-Besnier, Isabelle; De Waele, Liesbeth; Turnbull, Doug; Guglieri, Michela; Schrank, Bertold; Schoser, Benedikt; Seeger, Jurgen; Schreiber, Herbert; Glaeser, 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, Grainne S.; Hammans, Simon; Jackson, Andrew P.; Khan, Aijaz; Lane, Russell; McConville, John; McEntagart, Meriel; Al-Memar, 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; Lochmuller, Hanns.

    In: Human Mutation, Vol. 34, No. 8, 2013, p. 1111-1118.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - ANO5 gene analysis in a large cohort of patients with anoctaminopathy

    T2 - confirmation of male prevalence and high occurrence of the common exon 5 gene mutation

    AU - Sarkozy, Anna

    AU - Hicks, Debbie

    AU - Hudson, Judith

    AU - Laval, Steve H.

    AU - Barresi, Rita

    AU - Hilton-Jones, David

    AU - Deschauer, Marcus

    AU - Harris, Elizabeth

    AU - Rufibach, Laura

    AU - Hwang, Esther

    AU - Bashir, Rumaisa

    AU - Walter, Maggie C.

    AU - Krause, Sabine

    AU - van den Bergh, Peter

    AU - Illa, Isabel

    AU - Penisson-Besnier, Isabelle

    AU - De Waele, Liesbeth

    AU - Turnbull, Doug

    AU - Guglieri, Michela

    AU - Schrank, Bertold

    AU - Schoser, Benedikt

    AU - Seeger, Jurgen

    AU - Schreiber, Herbert

    AU - Glaeser, Dieter

    AU - Eagle, Michelle

    AU - Bailey, Geraldine

    AU - Walters, Richard

    AU - Longman, Cheryl

    AU - Norwood, Fiona

    AU - Winer, John

    AU - Muntoni, Francesco

    AU - Hanna, Michael

    AU - Roberts, Mark

    AU - Bindoff, Laurence A.

    AU - Brierley, Charlotte

    AU - Cooper, Robert G.

    AU - Cottrell, David A.

    AU - Davies, Nick P.

    AU - Gibson, Andrew

    AU - Gorman, Grainne S.

    AU - Hammans, Simon

    AU - Jackson, Andrew P.

    AU - Khan, Aijaz

    AU - Lane, Russell

    AU - McConville, John

    AU - McEntagart, Meriel

    AU - Al-Memar, Ali

    AU - Nixon, John

    AU - Panicker, Jay

    AU - Parton, Matt

    AU - Petty, Richard

    AU - Price, Christopher J.

    AU - Rakowicz, Wojtek

    AU - Ray, Partha

    AU - Schapira, Anthony H.

    AU - Swingler, Robert

    AU - Turner, Chris

    AU - Wagner, Kathryn R.

    AU - Maddison, Paul

    AU - Shaw, Pamela J.

    AU - Straub, Volker

    AU - Bushby, Kate

    AU - Lochmuller, Hanns

    PY - 2013

    Y1 - 2013

    N2 - 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.

    AB - 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.

    KW - PHENOTYPE

    KW - LGMD2L

    KW - 2L

    KW - GIRDLE MUSCULAR-DYSTROPHY

    KW - muscular dystrophy

    KW - gender

    KW - ANO5

    KW - MYOPATHY

    U2 - 10.1002/humu.22342

    DO - 10.1002/humu.22342

    M3 - Article

    VL - 34

    SP - 1111

    EP - 1118

    JO - Human Mutation

    JF - Human Mutation

    SN - 1059-7794

    IS - 8

    ER -