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

Authors

• Gabrielle Lemire, Department 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. Electronic address: glemire@cheo.on.ca.
• Aren E. Marshall, Department 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.
• Tejan S. Patel, Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
• Jonathan Trejo Martinez, Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
• Tally Lerman-Sagie, Fetal Neurology Multidisciplinary Center, Fetal Brain Research Center, Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel; Gray Faculty of Health and Medical Sciences, Tel Aviv University, Tel-Aviv, Israel.
• Wendy Mears, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.
• Xueqi Wang, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.
• Dorit Lev, Gray Faculty of Health and Medical Sciences, Tel Aviv University, Tel-Aviv, Israel; Institute of Medical Genetics, Fetal Neurology Multidisciplinary Center, Wolfson Medical Center, Holon, Israel.
• Alison J. Eaton, Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada.
• Kelly Bontempo, Advocate Health - MidwestFollow
• Brad Angle, Advocate Health - MidwestFollow
• Patrick Shannon, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
• Susan Blaser, Department of Diagnostic Imaging, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.

Recommended Citation

Lemire G, Marshall AE, Patel TS, et al. Bi-allelic variants in CDK20 cause a severe ciliopathy with midline brain and facial anomalies. Am J Hum Genet. Published online July 6, 2026. doi:10.1016/j.ajhg.2026.06.009

Affiliations

Advocate Children's Hospital, Chicago

Abstract

CDK20, also known as CCRK, is a cyclin-dependent kinase that regulates cell growth, primary cilium structure, and Sonic Hedgehog signaling. CDK20 has not yet been associated with a known human disorder. In this report, we present a cohort of seven individuals from five unrelated families with bi-allelic variants in CDK20 and an overlapping phenotype of ventriculomegaly or hydrocephalus, midline brain anomalies, abnormal nose, midline cleft lip and/or palate, cryptophthalmos or anophthalmia, postaxial polydactyly, and a sandal toe gap. Immunoblot analysis of fibroblasts derived from two affected fetuses with a homozygous CDK20 c.687+6T>C (p.?) variant demonstrated reduced CDK20 levels. Fibroblasts derived from these affected fetuses were also significantly deficient in cilium formation and function, with abnormal cilium morphology and significantly decreased Hedgehog responsiveness. Our findings support that bi-allelic loss-of-function variants in CDK20 cause a severe ciliopathy with midline brain and facial anomalies.

Document Type

Article

PubMed ID

42409022