|Title||CEP78 is mutated in a distinct type of Usher syndrome.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Fu, Q, Xu, M, Chen, X, Sheng, X, Yuan, Z, Liu, Y, Li, H, Sun, Z, Li, H, Yang, L, Wang, K, Zhang, F, Li, Y, Zhao, C, Sui, R, Chen, R|
|Journal||J Med Genet|
|Date Published||2016 Sep 14|
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.
|Alternate Journal||J. Med. Genet.|