Wolfram-like syndrome with bicuspid aortic valve due to a homozygous missense variant in CDK13

J Hum Genet. 2021 Oct;66(10):1009-1018. doi: 10.1038/s10038-021-00922-0. Epub 2021 Apr 21.

Abstract

Background: Wolfram syndrome (WFS) is characterized by deafness, diabetes mellitus, and diabetes insipidus along with optic atrophy. WFS has an autosomal recessive mode of inheritance and is due to variants in WFS1 and CISD2.

Methods: We evaluated the underlying molecular etiology of three affected members of a consanguineous family with hearing impairment, bicuspid aortic valve, diabetes mellitus and insipidus, clinodactyly, and gastrointestinal tract abnormalities via exome sequencing approach. We correlated clinical and imaging data with the genetic findings and their associated phenotypes.

Results: We identified a homozygous missense variant p.(Asn1097Lys) in CDK13, a gene previously associated with autosomal dominant congenital heart defects, dysmorphic facial features, clinodactyly, gastrointestinal tract abnormalities, intellectual developmental disorder, and seizures with variable phenotypic features.

Conclusion: We report a homozygous variant in CDK13 and suggest that this gene causes an autosomal recessive disorder with hearing impairment, bicuspid aortic valve, diabetes mellitus and insipidus, clinodactyly, and gastrointestinal tract abnormalities.

MeSH terms

  • Adolescent
  • Adult
  • Bicuspid Aortic Valve Disease / genetics
  • Bicuspid Aortic Valve Disease / pathology
  • CDC2 Protein Kinase / genetics*
  • Child
  • Child, Preschool
  • Consanguinity
  • Deafness / complications
  • Deafness / genetics*
  • Deafness / pathology
  • Diabetes Mellitus / genetics
  • Female
  • Gastrointestinal Tract / abnormalities
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / pathology
  • Genetic Predisposition to Disease*
  • Hearing Loss
  • Homozygote
  • Humans
  • Infant
  • Male
  • Mutation, Missense / genetics
  • Optic Atrophy / complications
  • Optic Atrophy / genetics*
  • Optic Atrophy / pathology
  • Wolfram Syndrome / complications
  • Wolfram Syndrome / epidemiology
  • Wolfram Syndrome / genetics*
  • Wolfram Syndrome / pathology
  • Young Adult

Substances

  • CDC2 Protein Kinase
  • CDK13 protein, human

Supplementary concepts

  • Wolfram-Like Syndrome, Autosomal Dominant