GUCY2D mutations in a Chinese cohort with autosomal dominant cone or cone-rod dystrophies

Background To report the results of the GUCY2D gene mutation analysis in a cohort of Chinese patients with cone or cone-rod dystrophies (COD or CORD) and to describe the clinical features observed in patients with molecularly confirmed COD or CORD. Methods A total of 74 probands clinically diagnosed with COD or CORD were recruited for genetic analysis; these included 15 unrelated patients with a positive family history consistent with an autosomal dominant pattern of inheritance and 59 unrelated sporadic cases. All probands underwent ophthalmic examinations including best-corrected visual acuity, fundus examination, optical coherence tomography, and electroretinography. Genomic DNA was extracted from venous blood of all participants, and all coding exons and exon-intron boundaries of the GUCY2D gene were screened for mutations by PCR-based DNA sequencing. Restriction fragment length polymorphism analysis and allele-specific PCR analysis were used to validate the substitution in all available family members. Results Four different GUCY2D missense mutations-three affected codon 838 and one affected codon 849-were identified in nine unrelated probands. Mutation p.R838H was identified in four probands, while both mutations p.R838C and p.R838P were found in two unrelated patients, and mutation p.T849A was found in one proband. The GUCY2D mutations were found in 47 % of the patients (7/15) with autosomal dominant cone dystrophy. Patients with mutation p.R838P presented a relatively severe clinical phenotype. Conclusion The GUCY2D mutations were frequent in Chinese families with autosomal dominant cone or cone-rod dystrophies. All mutations were found in exon 13, which should be given priority during mutation screening analysis.