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

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

agenesis development diabetes genetics mutation neonatal neurological pancreas

Journal

American journal of human genetics

ISSN: 1537-6605

Titre abrégé: Am J Hum Genet

Pays: United States

ID NLM: 0370475

Informations de publication

Date de publication:
02 05 2019

Historique:

received: 03 12 2018

accepted: 18 03 2019

pubmed: 23 4 2019

medline: 7 2 2020

entrez: 23 4 2019

Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.ajhg.2019.03.018 PMID: 31006513 PMC: PMC6506862

pubmed: 31006513

pii: S0002-9297(19)30114-4

doi: 10.1016/j.ajhg.2019.03.018

pmc: PMC6506862

pii:

doi:

Substances chimiques

CNOT1 protein, human 0

Transcription Factors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng