Two different genes for X-linked retinitis pigmentosa

Wirth, Brunhilde; Denton, M. J.; Chen, Jia-De; Neugebauer, M.; Halliday, F. B.; Schooneveld, Mary van; Donald, Jennifer A.; Bleeker‐Wagemakers, E. M.; Pearson, P. L.; Gal, Andreas

doi:10.1016/0888-7543(88)90011-0

Cited by 35 publications

(12 citation statements)

References 8 publications

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“…As far as heterozygotes are concerned, we were not able to observe the abnormal metallic sheen frequently reported in obligate carriers (Fishman et al 1986;Wirth et al 1988). It is important to emphasize, however, that the obligate carriers available for examination in our series were found to have either severe myopia or pigment deposits in their peripheral retina.…”

Section: Discussioncontrasting

confidence: 43%

“…The genetic heterogeneity of the disorder is also very marked since all modes of inheritance have been described and it is probable that several distinct genes are responsible for each form of inheritance (Berson et al 1980;Boughman et al 1980;Boughman and Caldwell 1982;Bunker et al 1984;Jay 1982). Indeed, at least two loci on the X chromosome have been identified (Wirth et al 1988;Wright et al 1989) and an early dominant form of RP has been recently mapped on chromosome 3 (McWilliam et al 1989). In order to contribute to gene mapping in RP, we tried to define clinically homogeneous samples of patients, especially stressing the different clinical patterns within each genetic subtype.…”

Section: Introductionmentioning

confidence: 99%

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Clinical and genetic heterogeneity in retinitis pigmentosa

et al. 1990

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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.

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Section: Discussioncontrasting

confidence: 43%

Section: Introductionmentioning

confidence: 99%

Clinical and genetic heterogeneity in retinitis pigmentosa

et al. 1990

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“…A milder phenotype is often present in female carriers, probably due to random X-inactivation. Close linkage of XLRP to markers DXS7 [Bhattacharya et al, 1984;Nussbaum et al, 1985] and OTC [Musarella et al, 1988;Chen et al, 1988;Denton et al, 1988;Wirth et al, 1988;Musarella et al, 1989] was found. Subsequent linkage analysis provided evidence for two different loci: RP2 (MIM# 312600) was positioned centromeric of DXS7, while RP3 (MIM# 312610) was telomeric of DXS7 and mapped between DXS1110 and OTC [Musarella et al, 1988;Chen et al, 1989;Musarella et al, 1990;Ott et al, 1990;Dahl et al, 1991].…”

Section: Introductionmentioning

confidence: 99%

Mutations ofRPGR in X-linked retinitis pigmentosa (RP3)

Vervoort

Wright

2002

Hum. Mutat.

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Mutations in RPGR, retinitis pigmentosa GTPase regulator, are associated with RP3 type of Xlinked retinitis pigmentosa, a severe, non-syndromic form of retinal degeneration. In the majority of subjects RPGR mutations are associated with a typical rod-cone degeneration, but in a small number, cone-rod dystrophy, deafness, and abnormalities in respiratory cilia have been noted. Alternative splicing of RPGR is complex in all species examined. In RP3 patients, mutations have been found in exons 1 14 and ORF15, thus delineating a transcript necessary for normal retinal function in humans. The great majority of mutations are predicted to result in premature termination of translation. These mutations are scattered over exons 1 14 and ORF15, while most missense mutations occur in a domain with homology to the protein RCC1, encoded by exons 1 10. Exon ORF15 is a hot spot for mutation, at least in the British population, in which it harbors 80% of the mutations found within a sample of 47 X-linked retinitis pigmentosa patients. Most RPGR mutations are unique to single families, which makes it difficult to demonstrate phenotype genotype correlations. Hum Mutat 19:486 500, 2002.

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“…A second Xlinked locus, RP3 (MIM No. 31261), has been mapped to Xp21.1-pll.4 in the vicinity of the OTC gene, based on two-point and multipoint linkage analyses and on consideration of specific recombination events that are incompatible with a locus proximal to DXS7 (Nussbaum et al 1985;Denton et al 1988;Wirth et al 1988a;Goonewardena et al 1988b;Musarella et al 1988). The possibility of yet a third X-linked RP locus or of an inversion should be considered to account for the observation of a single pedigree in which the RP mutation apparently maps distal to polymorphisms within the DMD ene (Musarella et al 1988).…”

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confidence: 99%