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

De Franco, Elisa; Watson, Rachel A; Weninger, Wolfgang J; Wong, Chi C; Flanagan, Sarah E; Caswell, Richard; Green, Angela; Tudor, Catherine; Lelliott, Christopher J; Geyer, Stefan H; Maurer-Gesek, Barbara; Reissig, Lukas F; Allen, Hana Lango; Caliebe, Almuth; Siebert, Reiner; Holterhus, Paul Martin; Deeb, Asma; Prin, Fabrice; Hilbrands, Robert; Heimberg, Harry; Ellard, Sian; Hattersley, Andrew T; Barroso, Inês

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

journal contribution

posted on 2020-01-06, 17:42 authored 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.