We identified three mutations of TBX1 in two unrelated patients without the 22q11.2 deletion-one with sporadic conotruncal anomaly face syndrome/velocardiofacial syndrome and one with sporadic DiGeorge's syndrome-and in three patients from a family with conotruncal anomaly face syndrome/velocardiofacial syndrome.
We identified three mutations of TBX1 in two unrelated patients without the 22q11.2 deletion-one with sporadic conotruncal anomaly face syndrome/velocardiofacial syndrome and one with sporadic DiGeorge's syndrome-and in three patients from a family with conotruncal anomaly face syndrome/velocardiofacial syndrome.
We identified three mutations of TBX1 in two unrelated patients without the 22q11.2 deletion-one with sporadic conotruncal anomaly face syndrome/velocardiofacial syndrome and one with sporadic DiGeorge's syndrome-and in three patients from a family with conotruncal anomaly face syndrome/velocardiofacial syndrome.
Mouse studies have shown that the Tbx1 gene is haploinsufficient, as expected for a DGS candidate gene, and that it is required for the development of pharyngeal arches and pouches, as predicted by the DGS clinical phenotype.
Our data show that haploinsufficiency of Tbx1 is sufficient to generate at least one important component of the DiGeorge syndrome phenotype in mice, and demonstrate the suitability of the mouse for the genetic dissection of microdeletion syndromes.
Tbx1 regulates fibroblast growth factors in the anterior heart field through a reinforcing autoregulatory loop involving forkhead transcription factors.