Biallelic variants in KIF14 cause intellectual disability with microcephaly

Area of Science:

• Genetics
• Developmental Biology
• Molecular Cell Biology

Background:

• Kinesin proteins are essential for intracellular transport and cell division.
• Dysfunctional kinesin family members are implicated in various human diseases, including cancer and monogenic disorders.

Observation:

• Eight individuals from four unrelated consanguineous families presented with intellectual disability and microcephaly.
• Homozygosity for pathogenic variants in KIF14, a mitotic motor protein, was identified in all affected individuals.

Findings:

• Identified four distinct likely pathogenic KIF14 variants: two loss-of-function (p.Asn83Ilefs*3, p.Ser1478fs) and two missense (p.Ser841Phe, p.Gly459Arg).
• KIF14 is crucial for the spindle localization of citron rho-interacting kinase (CIT), a protein also associated with microcephaly.
• Demonstrated KIF14's essential role in human development.

Implications:

• KIF14 is implicated as a causative gene for intellectual disability and microcephaly syndromes.
• The study reveals significant phenotypic variability associated with KIF14 mutations, ranging from fetal lethality to moderate developmental delay.
• These findings expand the understanding of genetic causes for neurodevelopmental disorders.