2. Academic Validation
  3. A Specific CNOT1 Mutation Results in a Novel Syndrome of Pancreatic Agenesis and Holoprosencephaly through Impaired Pancreatic and Neurological Development

A Specific CNOT1 Mutation Results in a Novel Syndrome of Pancreatic Agenesis and Holoprosencephaly through Impaired Pancreatic and Neurological Development

  • Am J Hum Genet. 2019 May 2;104(5):985-989. doi: 10.1016/j.ajhg.2019.03.018.
Elisa De Franco 1,  Rachel A Watson 2,  Wolfgang J Weninger 3,  Chi C Wong 2,  Sarah E Flanagan 1,  Richard Caswell 1,  Angela Green 2,  Catherine Tudor 2,  Christopher J Lelliott 2,  Stefan H Geyer 3,  Barbara Maurer-Gesek 3,  Lukas F Reissig 3,  Hana Lango Allen 1,  Almuth Caliebe 4,  Reiner Siebert 5,  Paul Martin Holterhus 6,  Asma Deeb 7,  Fabrice Prin 8,  Robert Hilbrands 9,  Harry Heimberg 10,  Sian Ellard 1,  Andrew T Hattersley 11,  Inês Barroso 12
Affiliations

Affiliations

  • 1 Institute of Biomedical and Clinical Science, University of Exeter Medical School, EX2 5DW Exeter, UK.
  • 2 Wellcome Sanger Institute, CB10 1SA Hinxton, UK.
  • 3 Centre for Anatomy and Cell Biology & MIC, Medical University of Vienna, 1090 Vienna, Austria.
  • 4 Institute of Human Genetics, Christian-Albrechts-University 24105 Kiel and University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
  • 5 Institute of Human Genetics, Christian-Albrechts-University 24105 Kiel and University Hospital Schleswig-Holstein, 24105 Kiel, Germany; Institute of Human Genetics, Ulm University & Ulm University Medical Center, 89081 Ulm, Germany.
  • 6 Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, Christian-Albrechts-University 24105 Kiel and University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
  • 7 Paediatric Endocrinology Department, Mafraq Hospital, 2951 Abu Dhabi, United Arab Emirates.
  • 8 The Francis Crick Institute, NW1 1ST London, UK.
  • 9 Vrije Universiteit Brussel, 1090 Brussels, Belgium; Universitair Ziekenhuis Brussel, 1090 Brussels, Belgium.
  • 10 Vrije Universiteit Brussel, 1090 Brussels, Belgium.
  • 11 Institute of Biomedical and Clinical Science, University of Exeter Medical School, EX2 5DW Exeter, UK. Electronic address: a.t.hattersley@exeter.ac.uk.
  • 12 Wellcome Sanger Institute, CB10 1SA Hinxton, UK. Electronic address: ines.barroso@mrc-epid.cam.ac.uk.
PMID: 31006513 DOI: 10.1016/j.ajhg.2019.03.018
Abstract

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.

Keywords

agenesis; development; diabetes; genetics; mutation; neonatal; neurological; pancreas.

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