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

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.