Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism
- 21 May 2006
- journal article
- letter
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 38 (6), 682-687
- https://doi.org/10.1038/ng1802
Abstract
We recently described a new neonatal diabetes syndrome associated with congenital hypothyroidism, congenital glaucoma, hepatic fibrosis and polycystic kidneys1. Here, we show that this syndrome results from mutations in GLIS3, encoding GLI similar 3, a recently identified transcription factor2. In the original family, we identified a frameshift mutation predicted to result in a truncated protein. In two other families with an incomplete syndrome, we found that affected individuals harbor deletions affecting the 11 or 12 5′-most exons of the gene. The absence of a major transcript in the pancreas and thyroid (deletions from both families) and an eye-specific transcript (deletion from one family), together with residual expression of some GLIS3 transcripts, seems to explain the incomplete clinical manifestations in these individuals. GLIS3 is expressed in the pancreas from early developmental stages, with greater expression in β cells than in other pancreatic tissues. These results demonstrate a major role for GLIS3 in the development of pancreatic β cells and the thyroid, eye, liver and kidney.Keywords
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