title: Whole-exome sequencing identifies USH2A mutations in a pseudo-dominant Usher syndrome family.
abstract: Usher syndrome (USH) is an autosomal recessive (AR) multi-sensory degenerative disorder leading to deaf-blindness. USH is clinically subdivided into three subclasses, and 10 genes have been identified thus far. Clinical and genetic heterogeneities in USH make a precise diagnosis difficult. A dominant‑like USH family in successive generations was identified, and the present study aimed to determine the genetic predisposition of this family. Whole‑exome sequencing was performed in two affected patients and an unaffected relative. Systematic data were analyzed by bioinformatic analysis to remove the candidate mutations via step‑wise filtering. Direct Sanger sequencing and co‑segregation analysis were performed in the pedigree. One novel and two known mutations in the USH2A gene were identified, and were further confirmed by direct sequencing and co‑segregation analysis. The affected mother carried compound mutations in the USH2A gene, while the unaffected father carried a heterozygous mutation. The present study demonstrates that whole‑exome sequencing is a robust approach for the molecular diagnosis of disorders with high levels of genetic heterogeneity.
authors: Department of Ophthalmology, The First Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors: Sui-Lian
authors: SL
authors: Zheng
authors: Anyang Eye Hospital, Anyang, Henan 455000, P.R. China.
authors: Hong-Liang
authors: HL
authors: Zhang
authors: The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China.
authors: Zhen-Lang
authors: ZL
authors: Lin
authors: Department of Ophthalmology, The First Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors: Qian-Yan
authors: QY
authors: Kang
mesh_terms: D059472:Exome; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005190:Family; D005260:Female; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D052245:Usher Syndromes / Q000235:genetics*
chemical_list: D016326:Extracellular Matrix Proteins; C112735:USH2A protein, human