1. Biallelic variants in KIF14 cause intellectual disability with microcephaly
- Author
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Tomasz Gambin, Stylianos E. Antonarakis, Jennifer McEvoy-Venneri, Najmeh Ahangari, Kiely N. James, Justyna Iwaszkiewicz, Amera Elbadawy, Shalini N. Jhangiani, Zeynep Coban Akdemir, Asbjørg Stray-Pedersen, Valentina Stanley, Federico Santoni, Vincent Zoete, Paul Hoff Backe, Reza Maroofian, Damir Musaev, Denice Belandres, Joseph G. Gleeson, Arvid Heiberg, Periklis Makrythanasis, James R. Lupski, Iman G Mahmoud, Mohammad Doosti, Laila Selim, Maha S. Zaki, Hanan Hamamy, Fatemeh Tara, Michel Guipponi, Ehsan Ghayoor Karimiani, and Hanne Sørmo Sorte
- Subjects
0301 basic medicine ,Microcephaly ,Mutation, Missense ,Kinesins ,Biology ,medicine.disease_cause ,Article ,03 medical and health sciences ,0302 clinical medicine ,Protein Domains ,Loss of Function Mutation ,Child ,Child, Preschool ,Female ,Humans ,Intellectual Disability/genetics ,Intellectual Disability/pathology ,Kinesin/chemistry ,Kinesin/genetics ,Kinesin/metabolism ,Microcephaly/genetics ,Microcephaly/pathology ,Oncogene Proteins/chemistry ,Oncogene Proteins/genetics ,Oncogene Proteins/metabolism ,Pedigree ,Phenotype ,Syndrome ,Intellectual Disability ,Intellectual disability ,Genetics ,medicine ,Missense mutation ,Mitosis ,Genetics (clinical) ,Oncogene Proteins ,Mutation ,medicine.disease ,3. Good health ,030104 developmental biology ,Kinesin ,Spindle localization ,030217 neurology & neurosurgery - 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.
- Published
- 2018