p.R270X MECP2 mutation and mortality in Rett syndrome

Among cases in the Australian Rett Syndrome Database, the nonsense mutation p.R270X is one of the most commonly occurring single pathogenic MECP2 mutations. In two recent published reports of the MECP2 mutational spectrum the p.R270X appeared to be under represented. We hypothesised that increased m...

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Main Authors: Jian, Le, Archer, H., Ravine, D., Kerr, A., De Klerk, N., Christodoulou, J., Bailey, M.
Format: Journal Article
Published: Nature Publishing Group 2005
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/17865
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author Jian, Le
Archer, H.
Ravine, D.
Kerr, A.
De Klerk, N.
Christodoulou, J.
Bailey, M.
author_facet Jian, Le
Archer, H.
Ravine, D.
Kerr, A.
De Klerk, N.
Christodoulou, J.
Bailey, M.
author_sort Jian, Le
building Curtin Institutional Repository
collection Online Access
description Among cases in the Australian Rett Syndrome Database, the nonsense mutation p.R270X is one of the most commonly occurring single pathogenic MECP2 mutations. In two recent published reports of the MECP2 mutational spectrum the p.R270X appeared to be under represented. We hypothesised that increased mortality arising from this mutation may underlie this apparent discrepancy. We investigated our hypothesis in two independent study groups from Australia and the UK with prospective data collections (total n=524). Only females with Rett syndrome and an identified MECP2 mutation were included. Significant differences in survival were detected among Rett syndrome cases grouped for the eight most frequent mutations (log-rank v2 (7)=15.71, P=0.03). Moreover, survival among cases with p.R270X, when compared with survival among cases with all the other mutations was reduced (log-rank v2 (2)=6.94, P=0.01). Our observation of a reduced survival associated with the p.R270X mutation offers an explanation for the under representation of p.R270X in older subjects with Rett syndrome.
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spelling curtin-20.500.11937-178652017-09-13T15:44:54Z p.R270X MECP2 mutation and mortality in Rett syndrome Jian, Le Archer, H. Ravine, D. Kerr, A. De Klerk, N. Christodoulou, J. Bailey, M. Rett syndrome MECP2 mutations p.R270X mortality Among cases in the Australian Rett Syndrome Database, the nonsense mutation p.R270X is one of the most commonly occurring single pathogenic MECP2 mutations. In two recent published reports of the MECP2 mutational spectrum the p.R270X appeared to be under represented. We hypothesised that increased mortality arising from this mutation may underlie this apparent discrepancy. We investigated our hypothesis in two independent study groups from Australia and the UK with prospective data collections (total n=524). Only females with Rett syndrome and an identified MECP2 mutation were included. Significant differences in survival were detected among Rett syndrome cases grouped for the eight most frequent mutations (log-rank v2 (7)=15.71, P=0.03). Moreover, survival among cases with p.R270X, when compared with survival among cases with all the other mutations was reduced (log-rank v2 (2)=6.94, P=0.01). Our observation of a reduced survival associated with the p.R270X mutation offers an explanation for the under representation of p.R270X in older subjects with Rett syndrome. 2005 Journal Article http://hdl.handle.net/20.500.11937/17865 10.1038/sj.ejhg.5201479 Nature Publishing Group unknown
spellingShingle Rett syndrome
MECP2 mutations
p.R270X
mortality
Jian, Le
Archer, H.
Ravine, D.
Kerr, A.
De Klerk, N.
Christodoulou, J.
Bailey, M.
p.R270X MECP2 mutation and mortality in Rett syndrome
title p.R270X MECP2 mutation and mortality in Rett syndrome
title_full p.R270X MECP2 mutation and mortality in Rett syndrome
title_fullStr p.R270X MECP2 mutation and mortality in Rett syndrome
title_full_unstemmed p.R270X MECP2 mutation and mortality in Rett syndrome
title_short p.R270X MECP2 mutation and mortality in Rett syndrome
title_sort p.r270x mecp2 mutation and mortality in rett syndrome
topic Rett syndrome
MECP2 mutations
p.R270X
mortality
url http://hdl.handle.net/20.500.11937/17865