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. Epub 2019 Apr 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Developmental Disabilities / etiology*
  • Developmental Disabilities / pathology
  • Embryo, Mammalian / metabolism
  • Embryo, Mammalian / pathology
  • Female
  • Holoprosencephaly / etiology*
  • Holoprosencephaly / pathology
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Newborn, Diseases / etiology*
  • Infant, Newborn, Diseases / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Mutation*
  • Nervous System Diseases / etiology*
  • Nervous System Diseases / pathology
  • Pancreas / abnormalities*
  • Pancreas / pathology
  • Pancreatic Diseases / congenital*
  • Pancreatic Diseases / etiology
  • Pancreatic Diseases / pathology
  • Pedigree
  • Phenotype
  • Sequence Homology
  • Syndrome
  • Transcription Factors / genetics*

Substances

  • CNOT1 protein, human
  • Transcription Factors

Supplementary concepts

  • Pancreatic Agenesis, Congenital