A recurrent mutation in GUCY2D associated with autosomal dominant cone dystrophy in a Chinese family

Mol Vis. 2011;17:3271-8. Epub 2011 Dec 15.


Purpose: To identify the genetic locus and mutation responsible for autosomal dominant cone dystrophy (adCOD) in a large Chinese family and to describe the phenotypes of the patients.

Methods: Genomic DNA and clinical data were collected from the family. Genome-wide linkage analysis was performed to map the disease locus, and Sanger dideoxy sequencing was used to detect the mutation in a candidate gene.

Results: Initially, genome-wide linkage analysis mapped the disease to 17p13.1 between D17S831 and D17S799, with a maximum lod score of 2.71 for D17S938 and D17S1852 at theta=0. Sequence analysis of the guanylate cyclase 2D gene (GUCY2D) in the linkage interval detected a recurrent heterozygous mutation, c.2513G>A (p.Arg838His). This mutation was present in all eight patients with adCOD, but neither in any of the six unaffected family members nor in 192 control chromosomes.

Conclusions: adCOD in this family is caused by a recurrent mutation in GUCY2D. adCOD can be detected in the first few years after birth in the family by fundus observation and electroretinogram recordings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian People
  • Case-Control Studies
  • Child, Preschool
  • Chromosomes, Human, Pair 17 / genetics*
  • DNA Mutational Analysis
  • Electroretinography
  • Female
  • Genetic Linkage
  • Genome-Wide Association Study
  • Genotype
  • Guanylate Cyclase / genetics*
  • Heterozygote
  • Humans
  • Lod Score
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Pedigree
  • Phenotype
  • Receptors, Cell Surface / genetics*
  • Retinitis Pigmentosa / diagnosis
  • Retinitis Pigmentosa / genetics*


  • Receptors, Cell Surface
  • guanylate cyclase 1
  • Guanylate Cyclase

Supplementary concepts

  • Retinal cone dystrophy 2