title: Targeted exome sequencing identified novel USH2A mutations in Usher syndrome families.
abstract: Usher syndrome (USH) is a leading cause of deaf-blindness in autosomal recessive trait. Phenotypic and genetic heterogeneities in USH make molecular diagnosis much difficult. This is a pilot study aiming to develop an approach based on next-generation sequencing to determine the genetic defects in patients with USH or allied diseases precisely and effectively. Eight affected patients and twelve unaffected relatives from five unrelated Chinese USH families, including 2 pseudo-dominant ones, were recruited. A total of 144 known genes of inherited retinal diseases were selected for deep exome resequencing. Through systematic data analysis using established bioinformatics pipeline and segregation analysis, a number of genetic variants were released. Eleven mutations, eight of them were novel, in the USH2A gene were identified. Biparental mutations in USH2A were revealed in 2 families with pseudo-dominant inheritance. A proband was found to have triple mutations, two of them were supposed to locate in the same chromosome. In conclusion, this study revealed the genetic defects in the USH2A gene and demonstrated the robustness of targeted exome sequencing to precisely and rapidly determine genetic defects. The methodology provides a reliable strategy for routine gene diagnosis of USH.
authors.affiliation: Division of Ophthalmic Genetics, Laboratory for Stem Cell & Retinal Regeneration, The Eye Hospital of Wenzhou Medical College, Wenzhou, China.
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Huang
authors.forename: Ping
authors.initials: P
authors.lastname: Xiang
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Dong-Jun
authors.initials: DJ
authors.lastname: Xing
authors.forename: Na
authors.initials: N
authors.lastname: Huang
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Min
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
authors.forename: Yi
authors.initials: Y
authors.lastname: Tong
authors.forename: Chi-Pui
authors.initials: CP
authors.lastname: Pang
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
authors.forename: Zi-Bing
authors.initials: ZB
authors.lastname: Jin
mesh_terms: D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D015203:Reproducibility of Results; D052245:Usher Syndromes / Q000175:diagnosis / Q000235:genetics*
chemical_list: D016326:Extracellular Matrix Proteins; C112735:USH2A protein, human