title: Genetic linkage analyses and Cx50 mutation detection in a large multiplex Chinese family with hereditary nuclear cataract.
abstract: OBJECTIVE
  The aim of the study was to characterize the underlying mutation in a large multiplex Chinese family with hereditary nuclear cataract.
  
  
  METHODS
  A 6-generation Chinese family having hereditary nuclear cataract was recruited and clinically verified. Blood DNA samples were obtained from 53 available family members. Linkage analyses were performed on the known candidate regions for hereditary cataract with 36 polymorphic microsatellite markers. To identify mutations related to cataract, a direct sequencing approach was applied to a candidate gene residing in our linkage locus.
  
  
  RESULTS
  A linkage locus was identified with a maximum 2-point LOD score of 4.31 (recombination fraction = 0) at marker D1S498 and a maximum multipoint LOD score of 5.7 between markers D1S2344 and D1S498 on chromosome 1q21.1, where the candidate gene Cx50 is located. Direct sequencing of Cx50 showed a 139 G to A transition occurred in all affected family members. This transitional mutation resulted in a replacement of aspartic acid by asparagine at residue 47 (D47N) and led to a loss-of-function of the protein.
  
  
  CONCLUSIONS
  The D47N mutation of Cx50 causes the hereditary nuclear cataract in this family in an autosomal dominant mode of inheritance with incomplete penetrance.
authors.affiliation: Shenyang He Eye Hospital, He College of Ophthalmology and Visual Science, Shenyang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Jiajing
authors.initials: J
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Qiushi
authors.initials: Q
authors.lastname: Dai
authors.forename: Hao
authors.initials: H
authors.lastname: Cui
authors.forename: Duen-Mei
authors.initials: DM
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Songnian
authors.initials: S
authors.lastname: Hu
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002386:Cataract / Q000235:genetics* / Q000473:pathology; D002681:China / Q000453:epidemiology; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D007907:Lens Nucleus, Crystalline / Q000473:pathology; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D000099264:Connexin 50
chemical_list: D017630:Connexins; D017931:DNA Primers; D005136:Eye Proteins; D000099264:Connexin 50