Identification of a novel missense mutation of MIP in a Chinese family with congenital cataracts by target region capture sequencing

Sci Rep. 2017 Jan 6;7:40129. doi: 10.1038/srep40129.

Abstract

Congenital cataract is both clinically diverse and genetically heterogeneous. To investigate the underlying genetic defect in three-generations of a Chinese family with autosomal dominant congenital cataracts, we recruited family members who underwent comprehensive ophthalmic examinations. A heterozygous missense mutation c.634G > C (p.G212R) substitution was identified in the MIP gene through target region capture sequencing. The prediction results of PolyPhen-2 and SIFT indicated that this mutation was likely to damage the structure and function of MIP. Confocal microscopy images showed that the intensity of the green fluorescent signal revealed much weaker signal from the mutant compared to the wild-type MIP. The expressed G212R-MIP was diminished and almost exclusively cytoplasmic in the HeLa cells; whereas the WT-MIP was stable dispersed throughout the cytoplasm, and it appeared to be in the membrane structure. Western blot analysis indicated that the protein expression level of the mutant form of MIP was remarkably reduced compared with that of the wild type, however, the mRNA levels of the wild-type and mutant cells were comparable. In conclusion, our study presented genetic and functional evidence for a novel MIP mutation of G212R, which leads to congenital progressive cortical punctate with or without Y suture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aquaporins / genetics*
  • Aquaporins / metabolism
  • Asian Continental Ancestry Group / genetics
  • Cataract / congenital*
  • Cataract / genetics*
  • Cataract / pathology
  • China
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism
  • Female
  • Humans
  • Male
  • Mutation, Missense*
  • Pedigree
  • RNA, Messenger / metabolism

Substances

  • Aquaporins
  • Eye Proteins
  • RNA, Messenger
  • aquaporin 0

Supplementary concepts

  • Cataract, Autosomal Dominant