title: Seven novel mutations in the long isoform of the USH2A gene in Chinese families with nonsyndromic retinitis pigmentosa and Usher syndrome Type II.
abstract: OBJECTIVE
  To describe the clinical and genetic findings in one Chinese family with autosomal recessive retinitis pigmentosa (arRP) and in three unrelated Chinese families with Usher syndrome type II (USH2).
  
  
  METHODS
  One family (FR1) with arRP and three unrelated families (F6, F7, and F8) with Usher syndrome (USH), including eight affected members and seven unaffected family individuals were examined clinically. The study included 100 normal Chinese individuals as normal controls. After obtaining informed consent, peripheral blood samples from all participants were collected and genomic DNA was extracted. Genotyping and haplotyping analyses were performed on the known genetic loci for arRP with a panel of polymorphic markers in family FR1. In all four families, the coding region (exons 2-72), including the intron-exon boundary of the USH2A (Usher syndrome type -2A protein) gene, was screened by PCR and direct DNA sequencing. Whenever substitutions were identified in a patient, a restriction fragment length polymorphism (RFLP) analysis, single strand conformation polymorphism (SSCP) analysis, or high resolution melt curve analysis (HRM) was performed on all available family members and on the 100 normal controls.
  
  
  RESULTS
  The affected individuals presented with typical fundus features of retinitis pigmentosa (RP), including narrowing of the vessels, bone-spicule pigmentation, and waxy optic discs. The electroretinogram (ERG) wave amplitudes of the available probands were undetectable. Audiometric tests in the affected individuals in family FR1 were normal, while indicating moderate to severe sensorineural hearing impairment in the affected individuals in families F6, F7, and F8. Vestibular function was normal in all patients from all four families. The disease-causing gene in family FR1 was mapped to the USH2A locus on chromosome 1q41. Seven novel mutations (two missenses, one 7-bp deletion, two small deletions, and two nonsenses) were detected in the four families after sequencing analysis of USH2A.
  
  
  CONCLUSIONS
  The results further support that mutations of USH2A are also responsible for non-syndromic RP. The mutation spectrum among Chinese patients might differ from that among European Caucasians.
authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Xu
authors.forename: Hanjun
authors.initials: H
authors.lastname: Dai
authors.forename: Tingting
authors.initials: T
authors.lastname: Lu
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.forename: Bing
authors.initials: B
authors.lastname: Dong
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D001299:Audiometry; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002878:Chromosomes, Human, Pair 1; D005091:Exons; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D056426:Genetic Loci; D005820:Genetic Testing; D005838:Genotype; D006239:Haplotypes; D034381:Hearing Loss; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D020033:Protein Isoforms / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics*; D017422:Sequence Analysis, DNA; D052245:Usher Syndromes / Q000235:genetics*
chemical_list: D016326:Extracellular Matrix Proteins; D020033:Protein Isoforms; C112735:USH2A protein, human