CNOT1 p.Arg535Cys variant in holoprosencephaly with late onset diabetes mellitus

Am J Med Genet A. 2024 Dec;194(12):e63836. doi: 10.1002/ajmg.a.63836. Epub 2024 Aug 16.

Abstract

Holoprosencephaly (HPE) results from a lack of cleavage of the prosencephalon. It has a complex etiology, resulting from chromosome abnormalities or single gene variants in the Sonic hedgehog signaling pathway. A single variant, p.Arg535Cys in CNOT1, has been described in HPE in association with pancreatic agenesis and neonatal diabetes. Here, we report on a case of HPE and p.Arg535Cys in CNOT1 without pancreatic agenesis where the patient presented with diabetes mellitus in adolescence. This case reinforces the role of CNOT1 in pancreatic development. We suggest that individuals with p.Arg535Cys in CNOT1 with no pancreas abnormalities observed at birth should be screened for diabetes during follow-up.

Keywords: CNOT1 gene; diabetes mellitus; holoprosencephaly.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Age of Onset
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / pathology
  • Female
  • Hedgehog Proteins / genetics
  • Holoprosencephaly* / genetics
  • Holoprosencephaly* / pathology
  • Humans
  • Male
  • Mutation / genetics
  • Pancreas / abnormalities
  • Pancreas / pathology
  • Phenotype

Substances

  • Hedgehog Proteins