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, A.; Hicks, D.; Hudson, J.; Laval, S.H.; Barresi, R.; Hilton-Jones, D.; Deschauer, M.; Harris, E.; Rufibach, L.; Hwang, E.; Bashir, R.; Walter, M.C.; 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, L.A.; Brierley, C.; Cooper, R.G.; Cottrell, D.A.; Davies, N.P.; Gibson, A.; Gorman, G.S.; Hammans, S.; Jackson, A.P.; Khan, A.; Lane, R.; McConville, J.; McEntagart, M.; Al-Memar, A.; Nixon, J.; Panicker, J.; Parton, M.; Petty, R.; Price, C.J.; Rakowicz, W.; Ray, P.; Schapira, A.H.; Swingler, R.; Turner, C.; Wagner, K.R.; Maddison, P.; Shaw, P.J.; Straub, V.; Bushby, K.; Lochmüller, H.

doi: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, A.; Hicks, D.; Hudson, J.; Laval, S.H.; Barresi, R.; Hilton-Jones, D.; Deschauer, M.; Harris, E.; Rufibach, L.; Hwang, E.; Bashir, R.; Walter, M.C.; 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, L.A.; Brierley, C.; Cooper, R.G.; Cottrell, D.A.; Davies, N.P.; Gibson, A.; Gorman, G.S.; Hammans, S.; Jackson, A.P.; Khan, A.; Lane, R.; McConville, J.; McEntagart, M.; Al-Memar, A.; Nixon, J.; Panicker, J.; Parton, M.; Petty, R.; Price, C.J.; Rakowicz, W.; Ray, P.; Schapira, A.H.; Swingler, R.; Turner, C.; Wagner, K.R.; Maddison, P.; Shaw, P.J.; Straub, V.; Bushby, K.; Lochmüller, H.

Authors

A. Sarkozy

D. Hicks

J. Hudson

S.H. Laval

R. Barresi

D. Hilton-Jones

M. Deschauer

E. Harris

L. Rufibach

E. Hwang

R. Bashir

M.C. Walter

S. Krause

P. van den Bergh

I. Illa

I. Pénisson-Besnier

L. De Waele

D. Turnbull

M. Guglieri

B. Schrank

B. Schoser

J. Seeger

H. Schreiber

D. Gläser

M. Eagle

G. Bailey

R. Walters

C. Longman

F. Norwood

J. Winer

F. Muntoni

M. Hanna

M. Roberts

L.A. Bindoff

C. Brierley

R.G. Cooper

D.A. Cottrell

N.P. Davies

A. Gibson

G.S. Gorman

S. Hammans

A.P. Jackson

A. Khan

R. Lane

J. McConville

M. McEntagart

A. Al-Memar

J. Nixon

J. Panicker

M. Parton

R. Petty

C.J. Price

W. Rakowicz

P. Ray

A.H. Schapira

R. Swingler

C. Turner

K.R. Wagner

P. Maddison

P.J. Shaw

V. Straub

K. Bushby

H. Lochmüller

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.

Citation

Sarkozy, A., Hicks, D., Hudson, J., Laval, S., Barresi, R., Hilton-Jones, D., …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: Variation, Informatics and Disease, 34(8), 1111-1118. https://doi.org/10.1002/humu.22342

Journal Article Type	Article
Publication Date	Aug 1, 2013
Deposit Date	Dec 18, 2014
Publicly Available Date	Apr 14, 2015
Journal	Human Mutation
Print ISSN	1059-7794
Electronic ISSN	1098-1004
Publisher	Wiley
Peer Reviewed	Peer Reviewed
Volume	34
Issue	8
Pages	1111-1118
DOI	https://doi.org/10.1002/humu.22342
Keywords	ANO5, LGMD2L, Gender, Muscular dystrophy.

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Copyright Statement
This is the accepted version of the following article: Sarkozy, A., Hicks, D., Hudson, J., Laval, S. H., Barresi, R., Hilton-Jones, D., Deschauer, M., Harris, E., Rufibach, L., Hwang, E., Bashir, R., Walter, M. C., 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, L. A., Brierley, C., Cooper, R. G., Cottrell, D. A., Davies, N. P., Gibson, A., Gorman, G. S., Hammans, S., Jackson, A. P., Khan, A., Lane, R., McConville, J., McEntagart, M., Al-Memar, A., Nixon, J., Panicker, J., Parton, M., Petty, R., Price, C. J., Rakowicz, W., Ray, P., Schapira, A. H., Swingler, R., Turner, C., Wagner, K. R., Maddison, P., Shaw, P. J., Straub, V., Bushby, K. and 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, 34 (8): 1111-1118, which has been published in final form at http://dx.doi.org/10.1002/humu.22342. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.