2. Academic Validation
  3. Genetic variants in the KDM6B gene are associated with neurodevelopmental delays and dysmorphic features

Genetic variants in the KDM6B gene are associated with neurodevelopmental delays and dysmorphic features

  • Am J Med Genet A. 2019 Jul;179(7):1276-1286. doi: 10.1002/ajmg.a.61173.
Elliot S Stolerman 1,  Elizabeth Francisco 1,  Jennifer L Stallworth 1,  Julie R Jones 1,  Kristin G Monaghan 2,  Jennifer Keller-Ramey 2,  Richard Person 2,  Ingrid M Wentzensen 2,  Kirsty McWalter 2,  Boris Keren 3,  Benedicte Heron 3,  Caroline Nava 3,  Delphine Heron 3,  Katherine Kim 4 5,  Barbara Burton 4 5,  Fatima Al-Musafri 6,  Lauren O'Grady 7,  Inderneel Sahai 7,  Luis F Escobar 8,  Marije Meuwissen 9,  Edwin Reyniers 9,  Frank Kooy 9,  Yves Lacassie 10 11,  Meral Gunay-Aygun 12,  Krista Sondergaard Schatz 12,  Ron Hochstenbach 13,  Petra J G Zwijnenburg 13,  Quinten Waisfisz 13,  Marjon van Slegtenhorst 14,  Grazia M S Mancini 14,  Raymond J Louie 1
Affiliations

Affiliations

  • 1 Greenwood Genetic Center, Greenwood, South Carolina.
  • 2 GeneDx, Gaithersburg, Maryland.
  • 3 APHP, Hôpital Armand Trousseau, Paris, France.
  • 4 Division of Genetics, Birth Defects and Metabolism, Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois.
  • 5 Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
  • 6 Pediatrics Department, Hamad Medical Corporation, Qatar.
  • 7 Massachusetts General Hospital, Boston, Massachusetts.
  • 8 Medical Genetics and Neurodevelopmental Center, Peyton Manning Children's, Hospital at St. Vincent, Indianapolis, Indiana.
  • 9 Medical Genetics, University of Antwerp, Antwerp, Belgium.
  • 10 Children's Hospital New Orleans, New Orleans, Louisiana.
  • 11 Louisiana State University Health Sciences Center, New Orleans, Louisiana.
  • 12 Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland.
  • 13 Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
  • 14 Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
PMID: 31124279 DOI: 10.1002/ajmg.a.61173
Abstract

Lysine-specific demethylase 6B (KDM6B) demethylates trimethylated lysine-27 on histone H3. The methylation and demethylation of histone proteins affects gene expression during development. Pathogenic alterations in histone lysine methylation and demethylation genes have been associated with multiple neurodevelopmental disorders. We have identified a number of de novo alterations in the KDM6B gene via whole exome sequencing (WES) in a cohort of 12 unrelated patients with developmental delay, intellectual disability, dysmorphic facial features, and other clinical findings. Our findings will allow for further investigation in to the role of the KDM6B gene in human neurodevelopmental disorders.

Keywords

KDM6B; demethylase; lysine; neurodevelopmental.

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