Clinical and genetic heterogeneity in retinitis pigmentosa

Abstract

The clinical course of defective vision and blindness has been investigated in relation to different modes of genetic transmission in a large series of 93 families with retinitis pigmentosa (RP). For autosomal dominant RP, two clinical subtypes could be distinguished according to the delay in macular involvement. In the severe form, macular involvement occurred within 10 years, while in the mild form, macular involvement occurred after 20 years. Interestingly, a significant increase of mean paternal age (38.8 years, mean controls in France = 29.1 years, P less than 0.001) was found in this form of RP, a feature which is suggestive of new mutations. For autosomal recessive RP, four significantly different clinical subtypes could be recognized, according to both age of onset and the pattern of development (P less than 0.001), namely cone-rod dystrophy and early-onset severe forms on the one hand (mean age of onset = 7.6 years), late-onset mild forms and senile forms on the other. Similarly, two significantly different clinical subtypes could be recognized in X-linked RP, according to both mode and age of onset, which were either myopia (mean age = 3.5 +/- 0.5 years) or night blindness (mean age = 10.6 +/- 4.1 years. P less than 0.001). By contrast, no difference was noted regarding the clinical course of the disease, which was remarkably severe whatever the clinical subtype (blindness before 25 years). In addition, all obligate carriers in our series were found to have either severe myopia or pigment deposits in their peripheral retina. Finally, sporadic RP represented the majority of cases in our series (42%). There was a considerable heterogeneity in this group, and at least three clinical forms could be recognized, namely cone-rod dystrophy, early onset-severe forms and late onset moderate forms. At the beginning of the disease, the hereditary nature of the sporadic forms was very difficult to ascertain (especially between 7-10 years) and only the clinical course could possibly provide information regarding the mode of inheritance. However, the high level of consanguinity, and the high sex ratio in early onset and severe sporadic forms (including cone-rod dystrophy), was suggestive of an autosomal or X-linked recessive inheritance, while increased paternal age in late onset forms was suggestive of autosomal dominant mutations.

Stargardt disease, Linkage to the ABCR gene region on 1p21‐p22 in Scandinavian families

“…S targardt disease (STGD; OMIM 248200) is a relatively rare recessive disorder, with a disease incidence of approximately 1:8000 -1:15000 (Blacharski 1988;Kaplan et al 1990). It is regarded to be one of the most frequent causes of macular degeneration in children, accounting for 7% of all retinal dystrophies (Stargardt 1909).…”

Contribution of SNRNP200 sequence variations to retinitis pigmentosa

“…5 These symptoms usually occur during the third decade, 6 although they can occur earlier depending on the inheritance pattern. 7 The fundus hallmarks include arteriolar attenuation, mid-peripheral perivascular bone-spicule pigmentation, tessellated fundus appearance, and waxy disc pallor. 8 RP can occur as a simplex disorder without known family history (35-50%) or inherit in autosomal dominant (ad) (10-30%), autosomal recessive (ar) (10-45%), and X-linked (xl) (0-15%) patterns.…”

Rescue of photoreceptor function by AAV-mediated gene transfer in a mouse model of inherited retinal degeneration

“…The ITRs are sufand reduced or absent electroretinogram. RP affects up ficient to ensure packaging of inserted DNA into infecto one in 3000 in the populations studied, 1,2 and is clinitious virions when AAV and adenoviral helper functions cally and genetically heterogeneous, with autosomal are provided in trans. As a potential vector for gene therdominant and recessive, as well as several X-linked apy, AAV has the further advantages that human infecforms.…”