Ocular phenotype of CORD5, an autosomal dominant retinal dystrophy associated with PITPNM3 p.Q626H mutation

Purpose: To describe in detail the phenotype of CORD5 in two families segregating a mutation c.1878G>C (p.Q626H) in the PITPNM3 gene. Methods: The study included 35 individuals from two different families of Swedish origin, all heterozygous for a PITPNM3 p.Q626H mutation. All participants underwent ophthalmological examination including kinetic perimetry, and in selected cases adaptometry, colour vision tests and optical coherence tomography (OCT). Electrophysiological studies were also performed. In some cases, the data were obtained from medical records. Results: The majority of patients showed subnormal visual acuity and light sensitivity from childhood. Early signs of macular degeneration were also observed. There was a progressive decrease in visual acuity leading to legal blindness in early adulthood. Electrophysiological testing showed a progressive loss of photoreceptor function restricted mainly to the cones. OCT revealed decreased macular thickness with flattened and enlarged fovea. Conclusion: Our observations of the PITPNM3 p.Q626H mutation carriers confirm that CORD5 is a disease not to mix with other retinal degenerations mapped to 17p13. The results of our clinical evaluation so far indicate that CORD5 is characterized by predominant cone dysfunction without signs of general involvement of the retinal pigment epithelium. The rod system also seems to be unaffected. In this sense, CORD5 is different from other autosomal dominant CORDs where rod involvement is present to some degree in a late phase of the disease. Some intra‐ and inter‐familial differences regarding the severity of the clinical picture were observed.