title: Exome sequencing of 18 Chinese families with congenital cataracts: a new sight of the NHS gene.
abstract: OBJECTIVE
  The aim of this study was to investigate the mutation spectrum and frequency of 34 known genes in 18 Chinese families with congenital cataracts.
  
  
  METHODS
  Genomic DNA and clinical data was collected from 18 families with congenital cataracts. Variations in 34 cataract-associated genes were screened by whole exome sequencing and then validated by Sanger sequencing.
  
  
  RESULTS
  Eleven candidate variants in seven of the 34 genes were detected by exome sequencing and then confirmed by Sanger sequencing, including two variants predicted to be benign and the other pathogenic mutations. The nine mutations were present in 9 of the 18 (50%) families with congenital cataracts. Of the four families with mutations in the X-linked NHS gene, no other abnormalities were recorded except for cataract, in which a pseudo-dominant inheritance form was suggested, as female carriers also had different forms of cataracts.
  
  
  CONCLUSIONS
  This study expands the mutation spectrum and frequency of genes responsible for congenital cataract. Mutation in NHS is a common cause of nonsyndromic congenital cataract with pseudo-autosomal dominant inheritance. Combined with our previous studies, a genetic basis could be identified in 67.6% of families with congenital cataracts in our case series, in which mutations in genes encoding crystallins, genes encoding connexins, and NHS are responsible for 29.4%, 14.7%, and 11.8% of families, respectively. Our results suggest that mutations in NHS are the common cause of congenital cataract, both syndromic and nonsyndromic.
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors: Wenmin
authors: W
authors: Sun
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors: Xueshan
authors: X
authors: Xiao
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors: Shiqiang
authors: S
authors: Li
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors: Xiangming
authors: X
authors: Guo
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors: Qingjiong
authors: Q
authors: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D044466:Asian People / Q000235:genetics*; D002386:Cataract / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D005260:Female; D023281:Genomics; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D017422:Sequence Analysis, DNA
chemical_list: D008565:Membrane Proteins; C488621:NHS protein, human; D009687:Nuclear Proteins