A substitution of arginine to lysine at the COOH-terminus of MIP caused a different binocular phenotype in a congenital cataract family

Mol Vis. 2007 Sep 30;13:1822-7.

Abstract

Purpose: To detect the cataractogenetic mutation for a six-generation family of Chinese origin with autosomal dominant binocular polymorphic cataracts.

Methods: A genome wide scan was performed using 382 fluorescent-labeled microsatellite markers. Multiple polymerase chain reaction (PCR) was performed according to the protocols previously described. Two-point linkage analysis was performed with the FASTLINK version of the MLINK in Linkage Program Package. The candidate gene was screened by direct sequencing.

Results: The disease locus was mapped to a 61 cM region on chromosome 12 defined by D12S310 and D12S351 near the major intrinsic protein gene (MIP). The maximum two-point lod score of 5.44 was obtained at marker D12S83 at theta=0.00. Direct sequencing of the encoding region of the candidate gene revealed a novel missense mutation G>A in exon 4 at nucleotide 702, which caused the replacement of arginine to lysine at codon 233 (p.R233K).

Conclusions: The change located in the alpha-helix domain of the COOH-terminus of MIP was determined to be associated with the binocular polymorphic cataract in this study. It suggests that arginine in this domain plays a crucial role in the function of the carboxyl-end of this protein and provides a helpful clue to further studies on completely understanding the physiological significance of MIP and its role in the formation of cataract.

MeSH terms

  • Amino Acid Substitution
  • Aquaporins / chemistry*
  • Aquaporins / genetics*
  • Arginine
  • Asian Continental Ancestry Group / genetics
  • Base Sequence
  • Cataract / congenital*
  • Cataract / genetics*
  • Cataract / pathology
  • Chromosome Mapping
  • Chromosomes, Human, Pair 12
  • Eye Proteins / chemistry*
  • Eye Proteins / genetics*
  • Female
  • Genetic Linkage
  • Haplotypes
  • Humans
  • Lod Score
  • Lysine
  • Male
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / genetics*
  • Molecular Sequence Data
  • Mutation, Missense
  • Pedigree
  • Phenotype
  • Protein Structure, Tertiary

Substances

  • Aquaporins
  • Eye Proteins
  • Membrane Glycoproteins
  • aquaporin 0
  • Arginine
  • Lysine