title: A novel NHS mutation causes Nance-Horan Syndrome in a Chinese family.
abstract: BACKGROUND
  Nance-Horan Syndrome (NHS) (OMIM: 302350) is a rare X-linked developmental disorder characterized by bilateral congenital cataracts, with occasional dental anomalies, characteristic dysmorphic features, brachymetacarpia and mental retardation. Carrier females exhibit similar manifestations that are less severe than in affected males.
  
  
  METHODS
  Here, we report a four-generation Chinese family with multiple affected individuals presenting Nance-Horan Syndrome. Whole-exome sequencing combined with RT-PCR and Sanger sequencing was used to search for a genetic cause underlying the disease phenotype.
  
  
  RESULTS
  Whole-exome sequencing identified in all affected individuals of the family a novel donor splicing site mutation (NM_198270: c.1045 + 2T > A) in intron 4 of the gene NHS, which maps to chromosome Xp22.13. The identified mutation results in an RNA processing defect causing a 416-nucleotide addition to exon 4 of the mRNA transcript, likely producing a truncated NHS protein.
  
  
  CONCLUSIONS
  The donor splicing site mutation NM_198270: c.1045 + 2T > A of the NHS gene is the causative mutation in this Nance-Horan Syndrome family. This research broadens the spectrum of NHS gene mutations, contributing to our understanding of the molecular genetics of NHS.
authors.affiliation: State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, Hunan, China.|Department of Biology, Allama Iqbal Open University, Islamabad, Pakistan.
authors.forename: Rizwana
authors.initials: R
authors.lastname: Kousar
authors.affiliation: State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: ChangSha Health Vocational Collage, Changsha, Hunan, China.
authors.forename: Fenglan
authors.initials: F
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Shenzhen Baoan District Maternal and Child Health Hospital, Shenzhen, Guangdong, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Zhigao
authors.initials: Z
authors.lastname: Long
authors.affiliation: State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Runyi
authors.initials: R
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.affiliation: Shenzhen Baoan District Maternal and Child Health Hospital, Shenzhen, Guangdong, China. lhy81048@hotmail.com.
authors.forename: Haiying
authors.initials: H
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, Hunan, China. panqian@sklmg.edu.cn.
authors.forename: Qian
authors.initials: Q
authors.lastname: Pan
mesh_terms: D044466:Asian People / Q000235:genetics*; D002386:Cataract / Q000151:congenital* / Q000235:genetics; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D022821:RNA Splice Sites; D017422:Sequence Analysis, DNA / Q000379:methods; D014071:Tooth Abnormalities / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C488621:NHS protein, human; D009687:Nuclear Proteins; D022821:RNA Splice Sites
keywords: Congenital cataract; Exome sequencing; RT-PCR; Sanger sequencing; Splice site