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Bi-allelic variants in CDK20 cause a severe ciliopathy with midline brain and facial anomalies

Gabrielle Lemire1, Aren E Marshall1, Tejan S Patel2

  • 1Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.

American Journal of Human Genetics
|July 6, 2026
PubMed

Insights

Bi-allelic variants in the CDK20 gene cause a severe ciliopathy. This condition is characterized by brain and facial abnormalities, highlighting CDK20

Area of Science:

  • Genetics
  • Developmental Biology
  • Cell Biology

Background:

  • Cyclin-dependent kinase 20 (CDK20), also known as CCRK, regulates crucial cellular processes including cell growth, primary cilium structure, and Sonic Hedgehog signaling.
  • CDK20 has not been previously linked to human disorders.
  • Ciliopathies are a group of genetic disorders affecting the primary cilium, often resulting in a wide range of developmental abnormalities.

Purpose of the Study:

  • To investigate the genetic basis of a severe developmental disorder characterized by midline brain and facial anomalies.
  • To determine the role of CDK20 in human development and disease.
  • To characterize the functional consequences of CDK20 variants on cilium formation and function.

Main Methods:

  • Clinical evaluation of seven individuals from five families with overlapping phenotypes.
  • Genetic analysis to identify bi-allelic variants in the CDK20 gene.
  • Immunoblot analysis of patient-derived fibroblasts to assess CDK20 protein levels.
  • Assessment of cilium formation, morphology, and function, including Hedgehog signaling responsiveness in patient-derived fibroblasts.

Main Results:

  • Identification of bi-allelic loss-of-function variants in CDK20 in all affected individuals.
  • Demonstration of reduced CDK20 protein levels in fibroblasts from affected fetuses.
  • Significant deficiencies in cilium formation and function, including abnormal morphology and decreased Hedgehog responsiveness, were observed in patient-derived fibroblasts.
  • The identified phenotype includes ventriculomegaly/hydrocephalus, midline brain anomalies, abnormal nose, midline cleft lip/palate, cryptophthalmos/anophthalmia, postaxial polydactyly, and a sandal toe gap.

Conclusions:

  • Bi-allelic loss-of-function variants in CDK20 cause a severe human ciliopathy.
  • CDK20 is essential for normal primary cilium formation and function, and its disruption leads to significant developmental defects, particularly affecting midline brain and facial structures.
  • This study establishes CDK20 as a novel disease-associated gene for ciliopathies.
Keywords:
CCRKCDK20ciliopathy

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