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A specific CNOT1 mutation results in a novel syndrome of pancreatic agenesis and holoprosencephaly through impaired pancreatic and neurological development.

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posted on 06.01.2020 by Elisa De Franco, Rachel A Watson, Wolfgang J Weninger, Chi C Wong, Sarah E Flanagan, Richard Caswell, Angela Green, Catherine Tudor, Christopher J Lelliott, Stefan H Geyer, Barbara Maurer-Gesek, Lukas F Reissig, Hana Lango Allen, Almuth Caliebe, Reiner Siebert, Paul Martin Holterhus, Asma Deeb, Fabrice Prin, Robert Hilbrands, Harry Heimberg, Sian Ellard, Andrew T Hattersley, Inês Barroso
We report a recurrent CNOT1 de novo missense mutation, GenBank: NM_016284.4; c.1603C>T (p.Arg535Cys), resulting in a syndrome of pancreatic agenesis and abnormal forebrain development in three individuals and a similar phenotype in mice. CNOT1 is a transcriptional repressor that has been suggested as being critical for maintaining embryonic stem cells in a pluripotent state. These findings suggest that CNOT1 plays a critical role in pancreatic and neurological development and describe a novel genetic syndrome of pancreatic agenesis and holoprosencephaly.

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