Further delineation of KIF21B-related neurodevelopmental disorders.

Autor: Narayanan DL; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India.; DBT/Wellcome Trust India Alliance Early Career Fellow, Manipal, India., Rivera Alvarez J; Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France.; Institut National de la Santé et de la Recherche Médicale, INSERM, U1258, Illkirch, France.; Université de Strasbourg, Strasbourg, France., Tilly P; Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France.; Institut National de la Santé et de la Recherche Médicale, INSERM, U1258, Illkirch, France.; Université de Strasbourg, Strasbourg, France., do Rosario MC; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Bhat V; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India., Godin JD; Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France. godin@igbmc.fr.; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France. godin@igbmc.fr.; Institut National de la Santé et de la Recherche Médicale, INSERM, U1258, Illkirch, France. godin@igbmc.fr.; Université de Strasbourg, Strasbourg, France. godin@igbmc.fr., Shukla A; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India. anju.shukla@manipal.edu.
Jazyk: angličtina
Zdroj: Journal of human genetics [J Hum Genet] 2022 Dec; Vol. 67 (12), pp. 729-733. Date of Electronic Publication: 2022 Oct 06.
DOI: 10.1038/s10038-022-01087-0
Abstrakt: Kinesin Family Member 21B (KIF21B) encoded by KIF21B (MIM*608322), belongs to the Kinesin superfamily proteins, which play a key role in microtubule organisation in neuronal dendrites and axons. Recently, heterozygous variants in KIF21B were implicated as the cause of intellectual disability and brain malformations in four unrelated individuals. We report a 9-year-old male with delayed speech, hyperactivity, poor social interaction, and autistic features. A parent-offspring trio exome sequencing identified a novel de novo rare heterozygous variant, NM_001252102.2: c.1513A>C, p.(Ser505Arg) in exon 11 of KIF21B. In vivo functional analysis using in utero electroporation in mouse embryonic cortex revealed that the expression of Ser505Arg KIF21B protein in the cerebral cortex impaired the radial migration of projection neurons, thus confirming the pathogenicity of the variant. Our report further validates pathogenic variants in KIF21B as a cause of neurodevelopmental disorder.
(© 2022. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)
Databáze: MEDLINE
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