Cone dystrophy affects the function of the retinal cones and is manifested as progressive loss of central vision, defective color vision, and photophobia. Kohn et al. (2007) examined members of a 5-generation Swedish family with cone dystrophy originally ... Cone dystrophy affects the function of the retinal cones and is manifested as progressive loss of central vision, defective color vision, and photophobia. Kohn et al. (2007) examined members of a 5-generation Swedish family with cone dystrophy originally reported by Balciuniene et al. (1995) and found that the majority of patients had subnormal visual acuity and light sensitivity from childhood, with early signs of macular degeneration and legal blindness by early adulthood. Electrophotoreceptor testing showed a progressive loss of photoreceptor function restricted to the cones. In a young patient, a bull's-eye maculopathy was seen, whereas in advanced cases, findings varied from pigment mottling to pronounced central choroidal atrophy. There was no peripheral restriction of visual fields and no history of nyctalopia. Photopic electroretinograms (ERGs) representing cone function were greatly diminished or absent, whereas scotopic ERGs showed normal amplitudes; the electrooculogram (EOG) was normal. Kohn et al. (2007) observed a milder phenotype in clinically examined members of a 7-generation Swedish family with cone dystrophy, including a woman who first presented with impaired vision at age 45 years, at which time she had defective color vision but a normal full-field cone response on electrophysiologic testing. Her daughter, who presented with low visual acuity, defective color vision, and light sensitivity at 30 years of age, had an abnormal ERG consistent with cone dystrophy.
In 2 multigenerational Swedish families with cone dystrophy mapping to chromosome 17p13, 1 of which was the family previously reported by Balciuniene et al. (1995), Kohn et al. (2007) sequenced the candidate gene PITPNM3 (608921) and identified heterozygosity ... In 2 multigenerational Swedish families with cone dystrophy mapping to chromosome 17p13, 1 of which was the family previously reported by Balciuniene et al. (1995), Kohn et al. (2007) sequenced the candidate gene PITPNM3 (608921) and identified heterozygosity for a Q626H mutation (608921.0001) that segregated with the disease in both families. The mutation was not found in 322 ethnically matched control chromosomes, or in 140 individuals with autosomal dominant or recessive retinitis pigmentosa (see 180100). Because of shared haplotypes and the presence of the Q626H mutation in both Swedish families, the authors suggested that the families had a common descent.