Cerulean cataract mapped to 12q13 and associated with a novel initiation codon mutation in MIP

Mol Vis. 2011:17:2049-55. Epub 2011 Jul 26.


Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aquaporins* / genetics
  • Asian People / genetics*
  • Base Sequence
  • Case-Control Studies
  • Cataract / congenital*
  • Cataract / genetics
  • Cataract / pathology
  • Chromosomes, Human, Pair 12
  • Codon, Initiator
  • DNA Mutational Analysis
  • Eye Proteins* / genetics
  • Female
  • Genes, Dominant
  • Genetic Linkage
  • Genome-Wide Association Study
  • Haplotypes
  • Heterozygote
  • Humans
  • Lens, Crystalline / metabolism*
  • Lens, Crystalline / pathology
  • Lod Score
  • Male
  • Molecular Sequence Data
  • Mutation
  • Pedigree


  • Aquaporins
  • Codon, Initiator
  • Eye Proteins
  • aquaporin 0

Supplementary concepts

  • Cerulean cataract