Biallelic variants in KIF14 cause intellectual disability with microcephaly.

TitleBiallelic variants in KIF14 cause intellectual disability with microcephaly.
Publication TypeJournal Article
Year of Publication2018
AuthorsMakrythanasis, P, Maroofian, R, Stray-Pedersen, A, Musaev, D, Zaki, MS, Mahmoud, IG, Selim, L, Elbadawy, A, Jhangiani, SN, Akdemir, ZHCoban, Gambin, T, Sorte, HS, Heiberg, A, McEvoy-Venneri, J, James, KN, Stanley, V, Belandres, D, Guipponi, M, Santoni, FA, Ahangari, N, Tara, F, Doosti, M, Iwaszkiewicz, J, Zoete, V, Backe, PHoff, Hamamy, H, Gleeson, JG, Lupski, JR, Karimiani, EGhayoor, Antonarakis, SE
JournalEur J Hum Genet
Date Published2018 03
KeywordsChild, Child, Preschool, Female, Humans, Intellectual Disability, Kinesin, Loss of Function Mutation, Microcephaly, Mutation, Missense, Oncogene Proteins, Pedigree, Phenotype, Protein Domains, Syndrome

Kinesin proteins are critical for various cellular functions such as intracellular transport and cell division, and many members of the family have been linked to monogenic disorders and cancer. We report eight individuals with intellectual disability and microcephaly from four unrelated families with parental consanguinity. In the affected individuals of each family, homozygosity for likely pathogenic variants in KIF14 were detected; two loss-of-function (p.Asn83Ilefs*3 and p.Ser1478fs), and two missense substitutions (p.Ser841Phe and p.Gly459Arg). KIF14 is a mitotic motor protein that is required for spindle localization of the mitotic citron rho-interacting kinase, CIT, also mutated in microcephaly. Our results demonstrate the involvement of KIF14 in development and reveal a wide phenotypic variability ranging from fetal lethality to moderate developmental delay and microcephaly.

Alternate JournalEur J Hum Genet
PubMed ID29343805
PubMed Central IDPMC5839044
Grant ListUM1 HG008900 / HG / NHGRI NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States

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