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 Pénisson-Besnier, Liesbeth De Waele, Doug Turnbull, Michela Guglieri, Bertold Schrank & 43 others Benedikt Schoser, Jürgen Seeger, Herbert Schreiber, Dieter Gläser, 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, Gráinne 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 Rae Wagner, Paul Maddison, Pamela J. Shaw, Volker Straub, Kate Bushby, Hanns Lochmüller

Research output: Contribution to journalArticle

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 (US)
Pages (from-to)1111-1118
Number of pages8
JournalHuman Mutation
Volume34
Issue number8
DOIs
StatePublished - Aug 2013

Fingerprint

Exons
Mutation
Genes
Lower Extremity
Phenotype
Recessive Genes
Muscular Dystrophies
Muscle Weakness
Alleles
Population
Muscular Dystrophy, Limb-Girdle, Type 2L

Keywords

  • ANO5
  • Gender
  • LGMD2L
  • Muscular dystrophy

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

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; Pénisson-Besnier, Isabelle; De 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; 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 Rae; Maddison, Paul; Shaw, Pamela J.; Straub, Volker; Bushby, Kate; Lochmüller, Hanns.

In: Human Mutation, Vol. 34, No. 8, 08.2013, p. 1111-1118.

Research output: Contribution to journalArticle

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, Pénisson-Besnier, I, De Waele, L, Turnbull, D, Guglieri, M, Schrank, B, Schoser, B, Seeger, J, Schreiber, H, Gläser, 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 & Lochmüller, 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
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 ; Pénisson-Besnier, Isabelle ; De 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 ; 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 Rae ; Maddison, Paul ; Shaw, Pamela J. ; Straub, Volker ; Bushby, Kate ; Lochmüller, 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.
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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.",
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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 - Pénisson-Besnier, Isabelle

AU - De Waele, Liesbeth

AU - Turnbull, Doug

AU - Guglieri, Michela

AU - Schrank, Bertold

AU - Schoser, Benedikt

AU - Seeger, Jürgen

AU - Schreiber, Herbert

AU - Gläser, 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, Gráinne 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 Rae

AU - Maddison, Paul

AU - Shaw, Pamela J.

AU - Straub, Volker

AU - Bushby, Kate

AU - Lochmüller, Hanns

PY - 2013/8

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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 - ANO5

KW - Gender

KW - LGMD2L

KW - Muscular dystrophy

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