PT - JOURNAL ARTICLE AU - Qing Fu AU - Mingchu Xu AU - Xue Chen AU - Xunlun Sheng AU - Zhisheng Yuan AU - Yani Liu AU - Huajin Li AU - Zixi Sun AU - Huiping Li AU - Lizhu Yang AU - Keqing Wang AU - Fangxia Zhang AU - Yumei Li AU - Chen Zhao AU - Ruifang Sui AU - Rui Chen TI - <em>CEP78</em> is mutated in a distinct type of Usher syndrome AID - 10.1136/jmedgenet-2016-104166 DP - 2017 Mar 01 TA - Journal of Medical Genetics PG - 190--195 VI - 54 IP - 3 4099 - http://jmg.bmj.com/content/54/3/190.short 4100 - http://jmg.bmj.com/content/54/3/190.full SO - J Med Genet2017 Mar 01; 54 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.