Biallelic variants in KIF14 cause intellectual disability with microcephaly

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

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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Female
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Kinesin / chemistry
  • Kinesin / genetics*
  • Kinesin / metabolism
  • Loss of Function Mutation
  • Microcephaly / genetics*
  • Microcephaly / pathology
  • Mutation, Missense
  • Oncogene Proteins / chemistry
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism
  • Pedigree
  • Phenotype
  • Protein Domains
  • Syndrome

Substances

  • Oncogene Proteins
  • KIF14 protein, human
  • Kinesin