title: Mutations in TBX1 genocopy the 22q11.2 deletion and duplication syndromes: a new susceptibility factor for mental retardation.
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.
authors: Section of Genetics, Hospital Universitari Son Dureta, Andrea Doria 55, Palma de Mallorca 07014, Balearic Islands, Spain.
authors: Laura
authors: L
authors: Torres-Juan
authors: Jordi
authors: J
authors: Rosell
authors: Montse
authors: M
authors: Morla
authors: Catalina
authors: C
authors: Vidal-Pou
authors: Fernando
authors: F
authors: García-Algas
authors: Maria-Angeles
authors: MA
authors: de la Fuente
authors: Miguel
authors: M
authors: Juan
authors: Albert
authors: A
authors: Tubau
authors: Daniel
authors: D
authors: Bachiller
authors: Marta
authors: M
authors: Bernues
authors: Angeles
authors: A
authors: Perez-Granero
authors: Nancy
authors: N
authors: Govea
authors: Xavier
authors: X
authors: Busquets
authors: Damian
authors: D
authors: Heine-Suñer
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D002353:Carrier State; D002648:Child; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D004062:DiGeorge Syndrome / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction / Q000379:methods; D020825:T-Box Domain Proteins / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D020825:T-Box Domain Proteins; C108625:TBX1 protein, human