Genes and Mutations in Autosomal Dominant Cone and Cone-Rod Dystrophy

Abstract

To date, mutations in ten genes have been described to cause autosomal dominant cone or cone-rod dystrophies; sometimes only a single report. Since a systematic investigation for these genes in patients with adCD and adCRD are lacking, we undertook a study to determine the prevalence and mutation spectrum of PRPH2, CRX, GUCA1A, GUCY2D, AIPL1, UNC119, PROM1 and PITPNM3 mutations in 52 unrelated patients and families with this rare diagnosis. We identified 15 different mutations in 25 families with adCD and adCRD: one patient carried a mutation in PROM1 (2%), 2 in CRX (4%), 4 in GUCA1A (8%), 6 in PRPH2 (11%) and 12 in GUCY2D (23%). Our analyses show that mutations in these genes account for ∼50% of all adCD and adCRD cases, while the other half still remains unsolved. No pathogenic variants were identified in AIPL1, UNC119 and PITPNM3 indicating that these only play a minor role in adCD and adCRD.