Splice site mutations in the ATP7A gene.
Menkes disease (MD) is caused by mutations in the ATP7A gene. We describe 33 novel splice site mutations detected in patients with MD or the milder phenotypic form, Occipital Horn Syndrome. We review these 33 mutations together with 28 previously published splice site mutations. We investigate 12 mu...
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2011-04-01
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doaj-16383d40f4644cdaa18427b801bfbe552020-11-25T02:23:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-04-0164e1859910.1371/journal.pone.0018599Splice site mutations in the ATP7A gene.Tina SkjørringeZeynep TümerLisbeth Birk MøllerMenkes disease (MD) is caused by mutations in the ATP7A gene. We describe 33 novel splice site mutations detected in patients with MD or the milder phenotypic form, Occipital Horn Syndrome. We review these 33 mutations together with 28 previously published splice site mutations. We investigate 12 mutations for their effect on the mRNA transcript in vivo. Transcriptional data from another 16 mutations were collected from the literature. The theoretical consequences of splice site mutations, predicted with the bioinformatics tool Human Splice Finder, were investigated and evaluated in relation to in vivo results. Ninety-six percent of the mutations identified in 45 patients with classical MD were predicted to have a significant effect on splicing, which concurs with the absence of any detectable wild-type transcript in all 19 patients investigated in vivo. Sixty-seven percent of the mutations identified in 12 patients with milder phenotypes were predicted to have no significant effect on splicing, which concurs with the presence of wild-type transcript in 7 out of 9 patients investigated in vivo. Both the in silico predictions and the in vivo results support the hypothesis previously suggested by us and others, that the presence of some wild-type transcript is correlated to a milder phenotype.http://europepmc.org/articles/PMC3073976?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tina Skjørringe Zeynep Tümer Lisbeth Birk Møller |
spellingShingle |
Tina Skjørringe Zeynep Tümer Lisbeth Birk Møller Splice site mutations in the ATP7A gene. PLoS ONE |
author_facet |
Tina Skjørringe Zeynep Tümer Lisbeth Birk Møller |
author_sort |
Tina Skjørringe |
title |
Splice site mutations in the ATP7A gene. |
title_short |
Splice site mutations in the ATP7A gene. |
title_full |
Splice site mutations in the ATP7A gene. |
title_fullStr |
Splice site mutations in the ATP7A gene. |
title_full_unstemmed |
Splice site mutations in the ATP7A gene. |
title_sort |
splice site mutations in the atp7a gene. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2011-04-01 |
description |
Menkes disease (MD) is caused by mutations in the ATP7A gene. We describe 33 novel splice site mutations detected in patients with MD or the milder phenotypic form, Occipital Horn Syndrome. We review these 33 mutations together with 28 previously published splice site mutations. We investigate 12 mutations for their effect on the mRNA transcript in vivo. Transcriptional data from another 16 mutations were collected from the literature. The theoretical consequences of splice site mutations, predicted with the bioinformatics tool Human Splice Finder, were investigated and evaluated in relation to in vivo results. Ninety-six percent of the mutations identified in 45 patients with classical MD were predicted to have a significant effect on splicing, which concurs with the absence of any detectable wild-type transcript in all 19 patients investigated in vivo. Sixty-seven percent of the mutations identified in 12 patients with milder phenotypes were predicted to have no significant effect on splicing, which concurs with the presence of wild-type transcript in 7 out of 9 patients investigated in vivo. Both the in silico predictions and the in vivo results support the hypothesis previously suggested by us and others, that the presence of some wild-type transcript is correlated to a milder phenotype. |
url |
http://europepmc.org/articles/PMC3073976?pdf=render |
work_keys_str_mv |
AT tinaskjørringe splicesitemutationsintheatp7agene AT zeyneptumer splicesitemutationsintheatp7agene AT lisbethbirkmøller splicesitemutationsintheatp7agene |
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