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.
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Expanding the genetics and phenotypes of ocular congenital cranial dysinnervation disorders.
Genet Med
July 2024
F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA; Department of Neurology, Boston Children's Hospital, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA; Department of Ophthalmology, Boston Children's Hospital, Boston, MA, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA, USA. Electronic address:
Article Synopsis
- This study aimed to identify the genetic causes and associations between genotype and phenotype in patients with unsolved ocular congenital cranial dysinnervation disorders (oCCDDs).
- Researchers analyzed data from 467 individuals with oCCDDs using exome or genome sequencing, revealing pathogenic variants in 43 probands and variants of uncertain significance in 70 others.
- The findings highlight the genetic diversity of oCCDDs and suggest that they may overlap with other genetic conditions, paving the way for further research on potential genetic links.
Rare and common variants associated with alcohol consumption identify a conserved molecular network.
Alcohol Clin Exp Res (Hoboken)
September 2024
Department of Psychiatry, University of California San Diego, La Jolla, California, USA.
Background: Genome-wide association studies (GWAS) have identified hundreds of common variants associated with alcohol consumption. In contrast, genetic studies of alcohol consumption that use rare variants are still in their early stages. No prior studies of alcohol consumption have examined whether common and rare variants implicate the same genes and molecular networks, leaving open the possibility that the two approaches might identify distinct biology.
View Article and Find Full Text PDFExpanding the genetics and phenotypes of ocular congenital cranial dysinnervation disorders.
medRxiv
March 2024
F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA.
Purpose: To identify genetic etiologies and genotype/phenotype associations for unsolved ocular congenital cranial dysinnervation disorders (oCCDDs).
Methods: We coupled phenotyping with exome or genome sequencing of 467 pedigrees with genetically unsolved oCCDDs, integrating analyses of pedigrees, human and animal model phenotypes, and variants to identify rare candidate single nucleotide variants, insertion/deletions, and structural variants disrupting protein-coding regions. Prioritized variants were classified for pathogenicity and evaluated for genotype/phenotype correlations.
Rare and Common Variants Associated with Alcohol Consumption Identify a Conserved Molecular Network.
bioRxiv
March 2024
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Genome-wide association studies (GWAS) have identified hundreds of common variants associated with alcohol consumption. In contrast, rare variants have only begun to be studied for their role in alcohol consumption. No studies have examined whether common and rare variants implicate the same genes and molecular networks.
View Article and Find Full Text PDFFurther delineation of KIF21B-related neurodevelopmental disorders.
J Hum Genet
December 2022
Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India.
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.
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