The authors have no competing financial interests or conflicts of interest to declare.
Exome sequencing identifies mutations in KIF14 as a novel cause of an autosomal recessive lethal fetal ciliopathy phenotype
Article first published online: 18 NOV 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
How to Cite
Exome sequencing identifies mutations in KIF14 as a novel cause of an autosomal recessive lethal fetal ciliopathy phenotype., , , , , , , , , , , , .
- Article first published online: 18 NOV 2013
- Accepted manuscript online: 15 OCT 2013 11:10AM EST
- Manuscript Revised: 11 OCT 2013
- Manuscript Accepted: 11 OCT 2013
- Manuscript Received: 17 AUG 2013
- British Columbia Clinical Genomics Network (BCCGN)
- Swiss Foundation for Grants in Biology and Medicine
- Swiss National Science Foundation (SFGBM/SNSF)
- Freie Akademische Gesellschaft (FAG) Basel
- autosomal recessive;
- exome sequencing;
Gene discovery using massively parallel sequencing has focused on phenotypes diagnosed postnatally such as well-characterized syndromes or intellectual disability, but is rarely reported for fetal disorders. We used family-based whole-exome sequencing in order to identify causal variants for a recurrent pattern of an undescribed lethal fetal congenital anomaly syndrome. The clinical signs included intrauterine growth restriction (IUGR), severe microcephaly, renal cystic dysplasia/agenesis and complex brain and genitourinary malformations. The phenotype was compatible with a ciliopathy, but not diagnostic of any known condition. We hypothesized biallelic disruption of a gene leading to a defect related to the primary cilium. We identified novel autosomal recessive truncating mutations in KIF14 that segregated with the phenotype. Mice with autosomal recessive mutations in the same gene have recently been shown to have a strikingly similar phenotype. Genotype–phenotype correlations indicate that the function of KIF14 in cell division and cytokinesis can be linked to a role in primary cilia, supported by previous cellular and model organism studies of proteins that interact with KIF14. We describe the first human phenotype, a novel lethal ciliary disorder, associated with biallelic inactivating mutations in KIF14. KIF14 may also be considered a candidate gene for allelic viable ciliary and/or microcephaly phenotypes.