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Eur J Hum Genet. 2018 Mar;26(3):330-339. doi: 10.1038/s41431-017-0088-9. Epub 2018 Jan 17.

Biallelic variants in KIF14 cause intellectual disability with microcephaly.

Author information

1
Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
2
Medical Research, RILD Welcome Wolfson Centre, Exeter Medical School, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
3
Genetics and Molecular Cell Sciences Research Centre, St George's University of London, Cranmer Terrace, London, SW17 0RE, UK.
4
Norwegian National Unit for Newborn Screening, Oslo University Hospital, Oslo, Norway.
5
Department of Pediatrics, Oslo University Hospital, Oslo, Norway.
6
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
7
Baylor-Hopkins Center for Mendelian Genomics of the Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.
8
Laboratory for Pediatric Brain Disease, Department of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, CA, 92093, USA.
9
Human Genetics and Genome Research Division, Clinical Genetics Department, National Research Centre, Cairo, Egypt.
10
Pediatric Neurology and Neurometabolic Unit, Pediatric Department, Cairo University Children Hospital, Cairo, Egypt.
11
Human Genome Sequencing Center of Baylor College of Medicine, Houston, TX, 77030, USA.
12
Institute of Computer Science, Warsaw University of Technology, Warsaw, Poland.
13
Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
14
Service of Genetic Medicine, University Hospitals of Geneva, Geneva, Switzerland.
15
Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
16
Department of Medical/Molecular Genetics, Hope Generation Genetic Polyclinic, Mashhad, Iran.
17
Women's Health Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
18
Molecular Modeling Group, Swiss Institute of Bioinformatics, Lausanne, Switzerland.
19
Department of Microbiology, Oslo University Hospital, Oslo, Norway.
20
Department of Medical Biochemistry, University of Oslo, Oslo, Norway.
21
Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, 77030, USA.
22
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.
23
Razavi Cancer Research Center, Razavi Hospital, Imam Reza International University, Mashhad, Iran.
24
Innovative Medical Research Center, Faculty of Medicine, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
25
Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland. Stylianos.Antonarakis@unige.ch.
26
Service of Genetic Medicine, University Hospitals of Geneva, Geneva, Switzerland. Stylianos.Antonarakis@unige.ch.
27
Institute of Genetics and Genomics of Geneva, Geneva, Switzerland. Stylianos.Antonarakis@unige.ch.

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.

PMID:
29343805
PMCID:
PMC5839044
DOI:
10.1038/s41431-017-0088-9
[Indexed for MEDLINE]
Free PMC Article

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