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
Volume26
Issue3
Pagination330-339
Date Published2018 Mar
ISSN1476-5438
Abstract

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.

DOI10.1038/s41431-017-0088-9
Alternate JournalEur. J. Hum. Genet.
PubMed ID29343805
PubMed Central IDPMC5839044
Grant ListP01 HD070494 / HD / NICHD NIH HHS / United States
R01 NS052455 / NS / NINDS NIH HHS / United States
UM1 HG006542 / HG / NHGRI NIH HHS / United States
UM1 HG008900 / HG / NHGRI NIH HHS / United States