Twenty-five novel mutations including duplications in the ATP7A gene.
Clin Genet
; 79(3): 243-53, 2011 Mar.
Article
de En
| MEDLINE
| ID: mdl-21208200
ABSTRACT
Twenty-five novel mutations including duplications in the ATP7A gene. Menkes disease (MD) and occipital horn syndrome (OHS) are allelic X-linked recessive copper deficiency disorders resulting from ATP7A gene mutations. MD is a severe condition leading to progressive neurological degeneration and death in early childhood, whereas OHS has a milder phenotype with mainly connective tissue abnormalities. Until now, molecular analyses have revealed only deletions and point mutations in both diseases. This study reports new molecular data in a series of 40 patients referred for either MD or OHS. We describe 23 point mutations (9 missense mutations, 7 splice site variants, 4 nonsense mutations, and 3 small insertions or deletions) and 7 intragenic deletions. Of these, 18 point mutations and 3 deletions are novel. Furthermore, our finding of four whole exon duplications enlarges the mutation spectrum in the ATP7A gene. ATP7A alterations were found in 85% of cases. Of these alterations, two thirds were point mutations and the remaining one third consisted of large rearrangements. We found that 66.6% of point mutations resulted in impaired ATP7A transcript splicing, a phenomenon more frequent than expected. This finding enabled us to confirm the pathogenic role of ATP7A mutations, particularly in missense and splice site variants.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Délétion de séquence
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Mutation ponctuelle
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Adenosine triphosphatases
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Duplication de gène
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Cutis laxa
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Transporteurs de cations
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Syndrome d'Ehlers-Danlos
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Maladie de Menkès
Limites:
Female
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Humans
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Male
Langue:
En
Journal:
Clin Genet
Année:
2011
Type de document:
Article