Retinitis Pigmentosa 73
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-73 (RP73) is caused by homozygous mutation in the HGSNAT gene (610453) on chromosome 8p11.
Mutation in the HGSNAT gene also causes mucopolysaccharidosis type IIIC (252930), the features of which include late-onset RP.
Clinical FeaturesHaer-Wigman et al. (2015) studied 3 affected individuals from 2 Ashkenazi Jewish Israeli families and 3 sibs from a Dutch family with nonsyndromic retinitis pigmentosa. All had night blindness and/or visual field loss as initial symptoms, but in the Israeli families, the 3 patients noted onset in childhood or adolescence and were diagnosed with RP in the fourth decade of life, whereas in the Dutch family, onset of symptoms did not occur until the fifth or sixth decade of life. The proband from the first Ashkenazi Jewish family was diagnosed at age 34 years, at which time full-field electroretinography (ERG) responses were undectectable. By age 60, her visual acuity was severely reduced bilaterally, and funduscopy showed severe and extensive atrophic changes of the retina and the retinal pigmented epithelium (RPE). In addition, choroidal sclerosis was observed, particularly at the posterior pole, accompanied by bone-spicule pigmentation at the midperiphery, with sparse and narrow retinal blood vessels. Examination of the 2 affected brothers from the other Ashkenazi family at ages 29 and 30 years showed reduced visual acuity, peripapillary atrophy, small macular crystals, and pronounced choroidal vasculature. Visual fields showed peripheral constriction bilaterally, and ERGs showed severe generalized rod-cone dysfunction with an electronegative pattern. In the Dutch family, 2 of the 3 affected sibs had reduced red color vision in addition to typical findings of retinitis pigmentosa. Comprehensive examination of affected individuals from all 3 families revealed no extraocular abnormalities, apart from mild hearing impairment at age 59 years in the Ashkenazi woman.
Molecular GeneticsIn a 60-year-old woman with nonsyndromic RP from a consanguineous Ashkenazi Jewish family, who was negative for several common founder mutations underlying RP in this population, Haer-Wigman et al. (2015) performed whole-exome sequencing and identified homozygosity for a missense mutation in the HGSNAT gene (R124W; 610453.0011) that segregated with disease in the family. Screening for the HGSNAT mutation in a panel of 66 Ashkenazi Jewish nonsyndromic RP patients who had previously been found negative for known RP-causing Ashkenazi Jewish founder mutations revealed 1 patient who was homozygous for R124W, which was not found in 211 controls of the same population. His affected brother was also homozygous for the mutation. In addition, whole-exome sequencing in 3 affected sibs from a Dutch family with RP identified homozygosity for a missense mutation (A615T; 610453.0012) as well as heterozygosity for another missense mutation (G133A; 610453.0013) in HGSNAT.