RT Journal Article SR Electronic T1 CEP78 is mutated in a distinct type of Usher syndrome JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 190 OP 195 DO 10.1136/jmedgenet-2016-104166 VO 54 IS 3 A1 Fu, Qing A1 Xu, Mingchu A1 Chen, Xue A1 Sheng, Xunlun A1 Yuan, Zhisheng A1 Liu, Yani A1 Li, Huajin A1 Sun, Zixi A1 Li, Huiping A1 Yang, Lizhu A1 Wang, Keqing A1 Zhang, Fangxia A1 Li, Yumei A1 Zhao, Chen A1 Sui, Ruifang A1 Chen, Rui YR 2017 UL http://jmg.bmj.com/content/54/3/190.abstract AB Background Usher syndrome is a genetically heterogeneous disorder featured by combined visual impairment and hearing loss. Despite a dozen of genes involved in Usher syndrome having been identified, the genetic basis remains unknown in 20–30% of patients. In this study, we aimed to identify the novel disease-causing gene of a distinct subtype of Usher syndrome.Methods Ophthalmic examinations and hearing tests were performed on patients with Usher syndrome in two consanguineous families. Target capture sequencing was initially performed to screen causative mutations in known retinal disease-causing loci. Whole exome sequencing (WES) and whole genome sequencing (WGS) were applied for identifying novel disease-causing genes. RT-PCR and Sanger sequencing were performed to evaluate the splicing-altering effect of identified CEP78 variants.Results Patients from the two independent families show a mild Usher syndrome phenotype featured by juvenile or adult-onset cone–rod dystrophy and sensorineural hearing loss. WES and WGS identified two homozygous rare variants that affect mRNA splicing of a ciliary gene CEP78. RT-PCR confirmed that the two variants indeed lead to abnormal splicing, resulting in premature stop of protein translation due to frameshift.Conclusions Our results provide evidence that CEP78 is a novel disease-causing gene for Usher syndrome, demonstrating an additional link between ciliopathy and Usher protein network in photoreceptor cells and inner ear hair cells.