title: Cerulean cataract mapped to 12q13 and associated with a novel initiation codon mutation in MIP.
abstract: OBJECTIVE
  To identify the genetic defect in a large Chinese family with autosomal dominant cerulean cataract.
  
  
  METHODS
  Genomic DNA and clinical data were collected from the family. Candidate gene sequencing and genome-wide linkage analysis were used to disclose the molecular basis responsible for cerulean cataract in the family.
  
  
  RESULTS
  Initially, sequencing analysis of the three genes (beta-B2-crystallin [CRYBB2], gamma-D-crystallin [CRYGD], and V-MAF avian musculoaponeurotic fibrosarcoma oncogene homolog [MAF]) known to cause cerulean cataract failed to find any mutation. Then, genome-wide linkage analysis mapped the disease to chromosome 12q13-q22 between D12S85 and D12S351, with a maximum lod score of 4.10 at θ=0. Sequence analysis of the major intrinsic protein of lens fiber gene (MIP), a gene known to cause other types of cataract in the linkage interval, detected a novel heterozygous initiation codon mutation, c.2T>C (p.Met1?). This mutation was present in all patients with cerulean cataract but was not present in any of the 13 unaffected family members nor in 96 control individuals.
  
  
  CONCLUSIONS
  Cerulean cataract was found in a large family and is caused by a novel initiation codon mutation in MIP. This study adds a new member in the existing list of genes causing cerulean cataract and expands the mutation spectrum and phenotypic association of MIP mutations.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xueshan
authors.initials: X
authors.lastname: Xiao
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Panfeng
authors.initials: P
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Li
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Jia
authors.forename: Wenmin
authors.initials: W
authors.lastname: Sun
authors.forename: Xiangming
authors.initials: X
authors.lastname: Guo
authors.forename: Qingjiong
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D020346:Aquaporins / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002386:Cataract / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D002881:Chromosomes, Human, Pair 12; D018387:Codon, Initiator; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism* / Q000473:pathology; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree
chemical_list: D020346:Aquaporins; D018387:Codon, Initiator; D005136:Eye Proteins; C030328:aquaporin 0