| First Author | Stoller JZ | Year | 2005 |
| Journal | Hum Mol Genet | Volume | 14 |
| Issue | 7 | Pages | 885-92 |
| PubMed ID | 15703190 | Mgi Jnum | J:98074 |
| Mgi Id | MGI:3577119 | Doi | 10.1093/hmg/ddi081 |
| Citation | Stoller JZ, et al. (2005) Identification of a novel nuclear localization signal in Tbx1 that is deleted in DiGeorge syndrome patients harboring the 1223delC mutation. Hum Mol Genet 14(7):885-92 |
| abstractText | DiGeorge syndrome (DGS) is the most common human chromosomal deletion syndrome and is frequently associated with deletions on chromosome 22q11. Approximately 17% of patients with the phenotypic features of this syndrome have no detectable genomic deletion. Animal studies using mouse models have implicated Tbx1 as a critical gene within the commonly deleted region, and several mutations in TBX1 have been identified recently in non-deleted patients, including missense and frameshift mutations. The mechanisms by which these mutations cause disease have remained unclear. We have identified a previously unrecognized and novel nuclear localization signal (NLS) at the C-terminus of Tbx1 that is deleted by the 1223delC mutation, thus explaining the mechanism of disease in these patients. This NLS is conserved across species, among a subfamily of T-box proteins including Brachyury and Tbx10, and among additional nuclear proteins. By providing functional data to indicate loss-of-function produced by the 1223delC TBX1 mutation, our results provide strong support for the conclusion that TBX1 mutations can cause DGS in humans. |
