Zuchner et al. (2011) studied an Ashkenazi Jewish family in which 3 of 4 sibs were diagnosed with retinitis pigmentosa (RP) in their teenage years. Early symptoms consisted of impaired night and peripheral vision. Clinical examination of the ... Zuchner et al. (2011) studied an Ashkenazi Jewish family in which 3 of 4 sibs were diagnosed with retinitis pigmentosa (RP) in their teenage years. Early symptoms consisted of impaired night and peripheral vision. Clinical examination of the affected individuals revealed pigmentary retinal degeneration, and the diagnosis of RP was confirmed by rod and cone responses on electroretinograms (ERGs). The remainder of the physical examination was unremarkable, and laboratory studies, including x-ray bone body survey and bone density scan, were all normal, although 2 of the affected sibs had a history of lytic bone disease diagnosed 15 years previously. Zelinger et al. (2011) examined 18 Ashkenazi Jewish patients with RP59 and observed a spectrum of findings, with visual acuities ranging from light perception to 20/20 vision. Funduscopic findings at various disease stages included waxy appearance of the optic nerve head, attenuation of retinal blood vessels, and bone spicule-like pigmentation. Optical coherence tomography (OCT) imaging in early disease showed preserved central retinal photoreceptors but a decline in photoreceptor layer thickness with distance from the fovea, and occasionally the presence of cystoid macular edema. Kinetic visual fields revealed reduced peripheral function in the youngest patients studied and only small central islands of vision remaining later in life. ERG responses were nondetectable in most patients.
In an Ashkenazi Jewish family in which 3 of 4 sibs had RP, Zuchner et al. (2011) screened all known RP genes but found no mutations. Whole-exome sequencing identified a single variant in the DHDDS gene (K42E; 608172.0001) ... In an Ashkenazi Jewish family in which 3 of 4 sibs had RP, Zuchner et al. (2011) screened all known RP genes but found no mutations. Whole-exome sequencing identified a single variant in the DHDDS gene (K42E; 608172.0001) that was present in homozygosity in the affected sibs but not present in their unaffected sib and for which the unaffected parents were heterozygous. Zuchner et al. (2011) stated that variant was likely to have arisen from an ancestral founder, as it was detected in heterozygosity in 8 of 717 Ashkenazi Jewish controls but was not found in 6,977 confirmed non-Ashkenazi white controls; the variant was also found once in 5,893 additional white controls for whom genomewide genotype data were not available. In 15 (12%) of 123 Ashkenazi Jewish (AJ) probands with RP, Zelinger et al. (2011) identified homozygosity for the K42E founder mutation. The K42E mutation was found in heterozygosity in 1 of 322 ethnically matched controls, indicating a carrier frequency of 0.3% in the AJ population; it was not detected in an additional set of 109 AJ patients with RP, in 20 AJ patients with other inherited retinal diseases, or in 70 patients with retinal degeneration of other ethnic origins.