title: Identification of a novel mutation in a Chinese family with Nance-Horan syndrome by whole exome sequencing.
abstract: OBJECTIVE
  Nance-Horan syndrome (NHS) is a rare X-linked disorder characterized by congenital nuclear cataracts, dental anomalies, and craniofacial dysmorphisms. Mental retardation was present in about 30% of the reported cases. The purpose of this study was to investigate the genetic and clinical features of NHS in a Chinese family.
  
  
  METHODS
  Whole exome sequencing analysis was performed on DNA from an affected male to scan for candidate mutations on the X-chromosome. Sanger sequencing was used to verify these candidate mutations in the whole family. Clinical and ophthalmological examinations were performed on all members of the family.
  
  
  RESULTS
  A combination of exome sequencing and Sanger sequencing revealed a nonsense mutation c.322G>T (E108X) in exon 1 of NHS gene, co-segregating with the disease in the family. The nonsense mutation led to the conversion of glutamic acid to a stop codon (E108X), resulting in truncation of the NHS protein. Multiple sequence alignments showed that codon 108, where the mutation (c.322G>T) occurred, was located within a phylogenetically conserved region. The clinical features in all affected males and female carriers are described in detail.
  
  
  CONCLUSIONS
  We report a nonsense mutation c.322G>T (E108X) in a Chinese family with NHS. Our findings broaden the spectrum of NHS mutations and provide molecular insight into future NHS clinical genetic diagnosis.
authors.affiliation: Department of Ophthalmology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen 518083, China; School of Basic Medical Sciences, Zhejiang University, Hangzhou 310058, China; Functional Genomics Center, Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, West Henrietta, NY 14586, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Hong
authors.forename: Yan-hua
authors.initials: YH
authors.lastname: Chen
authors.forename: Chen
authors.initials: C
authors.lastname: Xie
authors.forename: Bai-sheng
authors.initials: BS
authors.lastname: Xu
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Yue-qing
authors.initials: YQ
authors.lastname: Yang
authors.forename: Ying-ping
authors.initials: YP
authors.lastname: Huang
authors.forename: Jian-lian
authors.initials: JL
authors.lastname: Deng
authors.forename: Ming
authors.initials: M
authors.lastname: Qi
authors.forename: Yang-shun
authors.initials: YS
authors.lastname: Gu
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002386:Cataract / Q000151:congenital* / Q000235:genetics; D002681:China; D018389:Codon, Nonsense; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017386:Sequence Homology, Amino Acid; D014071:Tooth Abnormalities / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D008565:Membrane Proteins; C488621:NHS protein, human; D009687:Nuclear Proteins
keywords: Exome sequencing; Nance-Horan syndrome (NHS); X-linked disorder
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