Phenotypic heterogeneity associated with KIF21A: Two new cases and review of the literature.

TitlePhenotypic heterogeneity associated with KIF21A: Two new cases and review of the literature.
Publication TypeJournal Article
Year of Publication2024
AuthorsBhola, PT, Mishra, R, Posey, JE, Hamilton, LE, Graham, GE, Punetha, J, Lupski, JR, Boycott, KM, D'Amours, D, Kernohan, KD
Corporate AuthorsCare4Rare Canada Consortium
JournalAm J Med Genet A
Volume194
Issue3
Paginatione63455
Date Published2024 Mar
ISSN1552-4833
KeywordsHumans, Kinesins, Mutation, Nervous System Diseases, Phenotype
Abstract

Our understanding of genetic and phenotypic heterogeneity associated with the clinical spectrum of rare diseases continues to expand. Thorough phenotypic descriptions and model organism functional studies are valuable tools in dissecting the biology of the disease process. Kinesin genes are well known to be associated with specific disease phenotypes and a subset of kinesin genes, including KIF21A, have been associated with more than one disease. Here we report two patients with KIF21A variants identified by exome sequencing; one with biallelic variants, supporting a novel KIF21A related syndrome with recessive inheritance and the second report of this condition, and another with a heterozygous de novo variant allele representing a phenotypic expansion of the condition described to date. We provide detailed phenotypic information on both families, including a novel neuropathology finding of neuroaxonal dystrophy associated with biallelic variants in KIF21A. Additionally, we studied the dominant variant in Saccharomyces cerevisiae to assess variant pathogenicity and found that this variant appears to impair protein function. KIF21A associated disease has mounting evidence for phenotypic heterogeneity; further patients and study of an allelic series are required to define the phenotypic spectrum and further explore the molecular etiology for each of these conditions.

DOI10.1002/ajmg.a.63455
Alternate JournalAm J Med Genet A
PubMed ID37921537
Grant ListUM1 HG006542 / HG / NHGRI NIH HHS / United States
FDN-167265 / / CIHR / Canada
/ HL / NHLBI NIH HHS / United States
UM1 HG006542 / HG / NHGRI NIH HHS / United States
FDN-167265 / / CIHR / Canada
/ HL / NHLBI NIH HHS / United States
/ HG / NHGRI NIH HHS / United States

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