Clin Genet 2013 Printed in Singapore. All rights reserved  2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd CLINICAL GENETICS doi: 10.1111/cge.12301 Original Article Exome sequencing identifies mutations in KIF14 as a novel cause of an autosomal recessive lethal fetal ciliopathy phenotype Filges I, Nosova E, Bruder E, Tercanli S, Townsend K, Gibson WT, R¨ othlisberger B, Heinimann K, Hall JG, Gregory-Evans CY, Wasserman WW, Miny P, Friedman JM. Exome sequencing identifies mutations in KIF14 as a novel cause of an autosomal recessive lethal fetal ciliopathy phenotype. Clin Genet 2013.  John Wiley & Sons A/S. Published by John Wiley & Sons Ltd, 2013 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. Conflict of interest The authors have no competing financial interests or conflicts of interest to declare. I Filges a,b , E Nosova c ,E Bruder d , S Tercanli e ,K Townsend a , WT Gibson a ,B R¨ othlisberger f , K Heinimann b , JG Hall a , CY Gregory-Evans g , WW Wasserman c , P Miny b and JM Friedman a a Department of Medical Genetics, University of British Columbia, and Child and Family Research Institute, Vancouver, Canada, b Division of Medical Genetics, Department of Biomedicine, University Hospital, Basel, Switzerland, c Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada, d Department of Pathology, University Hospital, Basel, Switzerland, e Centre for Fetal Medicine and Ultrasound, Basel, Switzerland, f Department of Laboratory Medicine, Medical Genetics, Cantonal Hospital, Aarau, Switzerland, and g Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, Canada Key words: autosomal recessive – ciliopathy – cytokinesis – exome sequencing – fetal – KIF14 – lethal – prenatal Corresponding author: Isabel Filges, MD, Department of Medical Genetics, BC Children’s and Women’s Hospital, Box 153, 4480 Oak Street, Vancouver, BC V6H 3V4, Canada. Tel.: +001 604 875 2000×5625; fax: +001 604 875 3019; e-mail: ifilges@cfri.ca; Isabel.Filges@unibas.ch Received 17 August 2013, revised and accepted for publication 11 October 2013