Mutations in TBX1 genocopy the 22q11.2 deletion and duplication syndromes: a new susceptibility factor for mental retardation.
Eur J Hum Genet
; 15(6): 658-63, 2007 Jun.
Article
em En
| MEDLINE
| ID: mdl-17377518
ABSTRACT
A screen for TBX1 gene mutations identified two mutations in patients with some features compatible with the 22q11.2-deletion syndrome but with no deletions. One is a de novo missense mutation and the other is a 5' untranslated region (5'UTR) C>T change that affects a nucleotide with a remarkable trans-species conservation. Computer modelling shows that the 5'UTR change is likely to affect the mRNA structure and in vitro translation experiments demonstrate that it produces a twofold increase in translation efficiency. Recently, duplications in the 22q11.2 region were reported in patients referred for fragile-X determination because of cognitive and behavioural problems. Because the 5'UTR nucleotide change may be a functional equivalent of a duplication of the TBX1 gene, we decided to screen 200 patients who had been referred for fragile-X determination and 400 healthy control individuals. As a result, we found the 5'UTR mutation to be present in three patients with mental retardation or behavioural problems and absent in control individuals of the same ethnic background. This observation suggests that it may be reasonable to screen for such mutation among patients with unspecific cognitive deficits and we provide an easy and quick way to do it with an amplification refractory mutation system (ARMS) approach. To our knowledge, this is the first human mutation showing that TBX1 is a candidate causing mental retardation associated with the 22q11.2 duplication syndrome.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromossomos Humanos Par 22
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Proteínas com Domínio T
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Deficiência Intelectual
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Child
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Female
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Humans
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Male
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Newborn
Idioma:
En
Revista:
Eur J Hum Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Espanha