Retinitis Pigmentosa 67
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-67 (RP67) is caused by homozygous mutation in the NEK2 gene (604043) on chromosome 1q32. One such family has been reported.
DescriptionRetinitis pigmentosa (RP) is the name given to a group of hereditary retinal conditions in which degeneration of rod photoreceptors, responsible for vision under dark conditions, is more pronounced than that of cone photoreceptors, which mediate daylight vision. Individuals with RP typically experience night blindness at first, followed by progressive and unstoppable visual impairment in daytime conditions as well. Their visual fields become reduced gradually and sight is lost from the midperiphery to the periphery, then from the midperiphery to the center, resulting eventually in complete or near-complete blindness if left untreated. Most patients show intraretinal pigment in a bone-spicule configuration around the fundus periphery as well as retinal arteriolar attenuation, elevated final dark-adapted thresholds, and reduced and delayed electroretinograms. Autosomal recessive RP is the most common form of hereditary retinal degeneration in humans (summary by Nishiguchi et al., 2013).
For a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Molecular GeneticsNishiguchi et al. (2013) performed whole-genome sequencing in 16 unrelated RP patients from diverse ethnic backgrounds, and in 1 Japanese female patient, who did not have any clear-cut mutations in known RP genes, they identified a homozygous frameshift mutation in the NEK2 gene (604043.0001). The mutation was not detected in 1,273 Japanese and 95 North American controls, and inactivation of Nek2 in zebrafish induced retinal photoreceptor defects that were rescued by human NEK2 mRNA. Analysis of the NEK2 gene in a mixed cohort of 192 American and 64 Japanese RP patients, as well as in 13 patients with retinal degeneration who had previously shown linkage to the NEK2 region, identified a Japanese male patient with apparent autosomal recessive RP who was heterozygous for the same NEK2 frameshift mutation. However, he also carried a frameshift mutation in the known RP-associated RPGR gene (312610.0026) that had previously been described as a sufficient cause of X-linked RP (see 300029) by Vervoort et al. (2000); studies in zebrafish suggested that the RPGR allele interacts in trans with the NEK2 locus to exacerbate photoreceptor defects.