CDK13-related disorder: Report of a series of 18 previously unpublished individuals and description of an epigenetic signature - Sorbonne Université Access content directly
Journal Articles Genetics in Medicine Year : 2022

CDK13-related disorder: Report of a series of 18 previously unpublished individuals and description of an epigenetic signature

Flavien Rouxel
  • Function : Author
Raissa Relator
  • Function : Author
Jennifer Kerkhof
  • Function : Author
Haley Mcconkey
  • Function : Author
Michael Levy
  • Function : Author
Patricia Dias
  • Function : Author
Mouna Barat-Houari
  • Function : Author
Nathalie Bednarek
  • Function : Author
Odile Boute
  • Function : Author
Nicolas Chatron
  • Function : Author
Florian Cherik
  • Function : Author
Andrée Delahaye-Duriez
  • Function : Author
Martine Doco-Fenzy
Laurence Faivre
  • Function : Author
Lucas Gauthier
  • Function : Author
Michael Hildebrand
  • Function : Author
Gaëtan Lesca
  • Function : Author
James Lespinasse
  • Function : Author
Benoit Mazel
  • Function : Author
Leonie Menke
  • Function : Author
Angela Morgan
  • Function : Author
Lucile Pinson
  • Function : Author
Chloe Quelin
  • Function : Author
Massimiliano Rossi
  • Function : Author
Nathalie Ruiz-Pallares
  • Function : Author
Frederic Tran-Mau-Them
  • Function : Author
Imke van Kessel
  • Function : Author
Marie Vincent
  • Function : Author
Mathys Weber
  • Function : Author
Marjolaine Willems
  • Function : Author
Gwenael Leguyader
  • Function : Author
Bekim Sadikovic
  • Function : Author
David Genevieve

Abstract

Purpose Rare genetic variants in CDK13 are responsible for CDK13-related disorder (CDK13-RD), with main clinical features being developmental delay or intellectual disability, facial features, behavioral problems, congenital heart defect, and seizures. In this paper, we report 18 novel individuals with CDK13-RD and provide characterization of genome-wide DNA methylation. Methods We obtained clinical phenotype and neuropsychological data for 18 and 10 individuals, respectively, and compared this series with the literature. We also compared peripheral blood DNA methylation profiles in individuals with CDK13-RD, controls, and other neurodevelopmental disorders episignatures. Finally, we developed a support vector machine–based classifier distinguishing CDK13-RD and non–CDK13-RD samples. Results We reported health and developmental parameters, clinical data, and neuropsychological profile of individuals with CDK13-RD. Genome-wide differential methylation analysis revealed a global hypomethylated profile in individuals with CDK13-RD in a highly sensitive and specific model that could aid in reclassifying variants of uncertain significance. Conclusion We describe the novel features such as anxiety disorder, cryptorchidism, and disrupted sleep in CDK13-RD. We define a CDK13-RD DNA methylation episignature as a diagnostic tool and a defining functional feature of the evolving clinical presentation of this disorder. We also show overlap of the CDK13 DNA methylation profile in an individual with a functionally and clinically related CCNK-related disorder.

Dates and versions

hal-04587703 , version 1 (24-05-2024)

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Cite

Flavien Rouxel, Raissa Relator, Jennifer Kerkhof, Haley Mcconkey, Michael Levy, et al.. CDK13-related disorder: Report of a series of 18 previously unpublished individuals and description of an epigenetic signature. Genetics in Medicine, 2022, 24 (5), pp.1096-1107. ⟨10.1016/j.gim.2021.12.016⟩. ⟨hal-04587703⟩
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