Phenotypic characterization of a Chinese family with autosomal dominant cone-rod dystrophy related to GUCY2D

摘要

Background: This study aimed to evaluate the clinical phenotype and investigate the molecular genetic defect in a Chinese family with autosomal dominant cone-rod dystrophy (ADCRD). Methods: Family history was collected and patients underwent regular ophthalmologic examinations. Two affected individuals underwent three-year follow-ups to analyze the course of the disease. Venous blood was collected from family members and genomic DNA was extracted. A whole genome linkage analysis of 11 family members was performed using an Illumina Infinium Human Linkage-12 panel. All exons and exon-intron boundaries of guanylate cyclase 2D gene (GUCY2D) were sequenced for familial gene mutation. Results: Decreased visual acuity and photophobia usually commenced in early childhood in these patients. The family demonstrated an age-dependent increase in macular abnormalities with progressive development of geographic atrophy. Electrophysiological testing revealed a marked loss of cone function. Initially, a genome-wide linkage analysis mapped the disease to chromosome 17 (1-36 cM), with a maximum LOD score of 1.505. Sequence analysis of the GUCY2D gene in the linkage interval detected a recurrent heterozygous mutation, c.2513G > C (p.R838P). This mutation appeared in all seven patients with ADCRD but did not appear in any of the four unaffected family members. Conclusions: A missense mutation in the GUCY2D gene caused ADCRD in this family. Clinical follow-up of this family with a typical CRD phenotype revealed disease progression during the time period.