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
Wong, Chi C
Flanagan, Sarah E
Lelliott, Christopher J
Reissig, Lukas F
Holterhus, Paul Martin
Hattersley, Andrew T
American journal of human genetics
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De Franco, E., Watson, R. A., Weninger, W. J., Wong, C. C., Flanagan, S. E., Caswell, R., Green, A., et al. (2019). A Specific CNOT1 Mutation Results in a Novel Syndrome of Pancreatic Agenesis and Holoprosencephaly through Impaired Pancreatic and Neurological Development.. American journal of human genetics, 104 (5), 985-989. https://doi.org/10.1016/j.ajhg.2019.03.018
We report a recurrent CNOT1 de novo missense mutation, 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 which 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.
Pancreas, Animals, Mice, Knockout, Humans, Mice, Holoprosencephaly, Pancreatic Diseases, Nervous System Diseases, Infant, Newborn, Diseases, Syndrome, Transcription Factors, Pedigree, Developmental Disabilities, Amino Acid Sequence, Sequence Homology, Phenotype, Mutation, Infant, Infant, Newborn, Female, Male, Embryo, Mammalian
IB is funded by Wellcome (WT206194). ATH and SE are the recipients of a Wellcome Trust Senior Investigator award and ATH is employed as a core member of staff within the NIHR funded Exeter Clinical Research Facility and is an NIHR senior investigator. EDF was a Naomi Berrie Fellow in Diabetes Research during the study. SEF has a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number: 105636/Z/14/Z). CCW holds a Wellcome Trust Intermediate Clinical Fellowship (Grant Number: 105914/Z/14/Z). HH is funded by the Research Foundation-Flanders (FWO), the VUB Research Council and Stichting Diabetes Onderzoek Nederland.
External DOI: https://doi.org/10.1016/j.ajhg.2019.03.018
This record's URL: https://www.repository.cam.ac.uk/handle/1810/290948
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