Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism

Valérie Senée, Claude Chelala, Sabine Duchatelet, Daorong Feng, Hervé Blanc, Jack Christophe Cossec, Céline Charon, Marc Nicolino, Pascal Boileau, Douglas R. Cavener, Pierre Bougnères, Doris Taha, Cécile Julier

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Abstract

We recently described a new neonatal diabetes syndrome associated with congenital hypothyroidism, congenital glaucoma, hepatic fibrosis and polycystic kidneys. Here, we show that this syndrome results from mutations in GLIS3, encoding GLI similar 3, a recently identified transcription factor. 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.

Original languageEnglish (US)
Pages (from-to)682-687
Number of pages6
JournalNature Genetics
Volume38
Issue number6
DOIs
StatePublished - Jun 1 2006
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics

Cite this

Senée, V., Chelala, C., Duchatelet, S., Feng, D., Blanc, H., Cossec, J. C., Charon, C., Nicolino, M., Boileau, P., Cavener, D. R., Bougnères, P., Taha, D., & Julier, C. (2006). Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism. Nature Genetics, 38(6), 682-687. https://doi.org/10.1038/ng1802