PMID- 17377518
OWN - NLM
STAT- MEDLINE
DCOM- 20070716
LR  - 20111117
IS  - 1018-4813 (Print)
IS  - 1018-4813 (Linking)
VI  - 15
IP  - 6
DP  - 2007 Jun
TI  - Mutations in TBX1 genocopy the 22q11.2 deletion and duplication syndromes: a new 
      susceptibility factor for mental retardation.
PG  - 658-63
AB  - 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.
FAU - Torres-Juan, Laura
AU  - Torres-Juan L
AD  - Section of Genetics, Hospital Universitari Son Dureta, Andrea Doria 55, Palma de 
      Mallorca 07014, Balearic Islands, Spain.
FAU - Rosell, Jordi
AU  - Rosell J
FAU - Morla, Montse
AU  - Morla M
FAU - Vidal-Pou, Catalina
AU  - Vidal-Pou C
FAU - Garcia-Algas, Fernando
AU  - Garcia-Algas F
FAU - de la Fuente, Maria-Angeles
AU  - de la Fuente MA
FAU - Juan, Miguel
AU  - Juan M
FAU - Tubau, Albert
AU  - Tubau A
FAU - Bachiller, Daniel
AU  - Bachiller D
FAU - Bernues, Marta
AU  - Bernues M
FAU - Perez-Granero, Angeles
AU  - Perez-Granero A
FAU - Govea, Nancy
AU  - Govea N
FAU - Busquets, Xavier
AU  - Busquets X
FAU - Heine-Suner, Damian
AU  - Heine-Suner D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070321
PL  - England
TA  - Eur J Hum Genet
JT  - European journal of human genetics : EJHG
JID - 9302235
RN  - 0 (5' Untranslated Regions)
RN  - 0 (T-Box Domain Proteins)
RN  - 0 (TBX1 protein, human)
SB  - IM
MH  - 5' Untranslated Regions/genetics
MH  - Adolescent
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Carrier State
MH  - Child
MH  - Chromosomes, Human, Pair 22/*genetics
MH  - DNA Mutational Analysis/methods
MH  - DiGeorge Syndrome/genetics
MH  - Female
MH  - Gene Deletion
MH  - Humans
MH  - Infant, Newborn
MH  - Intellectual Disability/*genetics
MH  - Male
MH  - Molecular Sequence Data
MH  - Mutation, Missense
MH  - Polymerase Chain Reaction/methods
MH  - T-Box Domain Proteins/*genetics
EDAT- 2007/03/23 09:00
MHDA- 2007/07/17 09:00
CRDT- 2007/03/23 09:00
PHST- 2007/03/23 09:00 [pubmed]
PHST- 2007/07/17 09:00 [medline]
PHST- 2007/03/23 09:00 [entrez]
AID - 5201819 [pii]
AID - 10.1038/sj.ejhg.5201819 [doi]
PST - ppublish
SO  - Eur J Hum Genet. 2007 Jun;15(6):658-63. doi: 10.1038/sj.ejhg.5201819. Epub 2007 
      Mar 21.