MAFA missense mutation causes familial insulinomatosis and diabetes mellitus
Abstract
We report a disease-causing mutation in the β-cell-enriched MAFA transcription factor. Strikingly, the missense p.Ser64Phe MAFA mutation was associated with either of two distinct phenotypes, multiple insulin-producing neuroendocrine tumors of the pancreas—a condition known as insulinomatosis—or diabetes mellitus, recapitulating the physiological properties of MAFA both as an oncogene and as a key islet β-cell transcription factor. The implication of MAFA in these human phenotypes will provide insights into how this transcription factor regulates human β-cell activity as well as into the mechanisms of Maf-induced tumorigenesis.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- January 2018
- DOI:
- 10.1073/pnas.1712262115
- Bibcode:
- 2018PNAS..115.1027I