is mutated in a distinct type of Usher syndrome.

Title is mutated in a distinct type of Usher syndrome.
Publication TypeJournal Article
Year of Publication2017
AuthorsFu, 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
JournalJ Med Genet
Date Published2017 Mar
KeywordsAdult, Cell Cycle Proteins, Child, Consanguinity, Exome, Female, Frameshift Mutation, Genome, Human, Hair Cells, Auditory, Inner, High-Throughput Nucleotide Sequencing, Homozygote, Humans, Male, Pedigree, Retinitis Pigmentosa, Usher Syndromes

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 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 . 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 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 JournalJ Med Genet
PubMed ID27627988
PubMed Central IDPMC6235689
Grant ListP30 EY002520 / EY / NEI NIH HHS / United States
R01 EY018571 / EY / NEI NIH HHS / United States
R01 EY022356 / EY / NEI NIH HHS / United States
S10 RR026550 / RR / NCRR NIH HHS / United States

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