Mutations in the coding regions of TBX1 gene have been associated to 22q11 deletion syndrome with cardiac defects and isolated CHD cases, including ventricular septal defect (VSD).
This hypomorphic Tbx1 allele per se results in defects resembling 22q11DS but with a low penetrance of hallmark craniofacial malformations, unless chordin is mutant.
A study has also shown that phenotypic features of 22q11 deletion syndrome (22q11DS) were segregated with an inactivating mutation of TBX1 in one family, suggesting that the TBX1 gene plays a role in the pathogenesis of some psychiatric disorders.
Based on these results we conclude that TBX1 variation does not make a strong contribution to the genetic etiology of nonsyndromic forms of psychiatric disorders commonly seen in patients with 22q11DS.
A likely role for Tbx1 haploinsufficiency in psychiatric disease is further suggested by the identification of a family in which the phenotypic features of 22q11DS, including psychiatric disorders, segregate with an inactivating mutation of TBX1.
22q11 deletion syndrome (22qDS), also known as DiGeorge or velocardiofacial syndrome (DGS/VCFS), is a relatively common genetic anomaly that results in malformations of the heart, face and limbs.
Twenty children and young adults (age range 5 to 33 years, 12 females and eight males) with genetically confirmed 22q11 deletion syndrome (CATCH 22: Cardiac anomaly, Anomalous face, Thymus hypoplasia/aplasia, Cleft palate, and Hypocalcaemia), recruited from a large ongoing study, were given comprehensive assessments with a view to determining the pattern of neuropsychiatric and neuropsychological deficits thought to be part of the syndrome in many cases.