Mutations in TBX1 genocopy the 22q11.2 deletion and duplication syndromes: a new susceptibility factor for mental retardation
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...
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Veröffentlicht in: | European journal of human genetics : EJHG 2007-06, Vol.15 (6), p.658-663 |
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Sprache: | eng |
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Zusammenfassung: | 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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ISSN: | 1018-4813 1476-5438 |
DOI: | 10.1038/sj.ejhg.5201819 |