X-linked Retinitis Pigmentosa Profile of Clinical Findings

Fishman, Gerald A.; Farber, Marilyn D.; Derlacki, Deborah J.

doi:10.1001/archopht.1988.01060130395029

Cited by 112 publications

(81 citation statements)

References 16 publications

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“…It is consistent with the inference that most RP3 mutations are of independent origin. 24 Different clinical presentations have been recognised in XLRP, 3 and some genotype-phenotype correlations have been attempted in hemizygous males and heterozygous carrier female in XLRP families. [25][26][27]15 The location and nature of RPGR mutations might help to understand the molecular basis of XLRP and the role of the RPGR protein in photoreceptor function.…”

Section: Discussionsupporting

confidence: 43%

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Mutation analysis of the RPGR gene reveals novel mutations in south European patients with X-linked retinitis pigmentosa

et al. 1999

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The RPGR (retinitis pigmentosa GTPase regulator) gene has been shown to be mutated in 10-20% of patients with X-linked retinitis pigmentosa (XLRP), a severe form of inherited progressive retinal degeneration. A total of 29 different RPGR mutations have been identified in northern European and United States patients. We have performed mutation analysis of the RPGR gene in a cohort of 49 southern European males affected with XLRP. By multiplex SSCA and automatic direct sequencing of all 19 RPGR exons, seven different and novel mutations were identified in eight of the 49 families; these include three splice site mutations, two microdeletions, and two missense mutations. RNA analysis showed that the three splice site defects resulted in the generation of aberrant RPGR transcripts. Six of these mutations were detected in the conserved amino-terminal region of RPGR protein, containing tandem repeats homologous to the RCC1 protein, a guanine nucleotide-exchange factor for RanGTPase. Several exonic and intronic sequence variations were also detected. None of the RPGR mutations reported in other populations were identified in our series. Our results are consistent with the notions of heterogeneity and minority causation of XLRP by mutations in RPGR in Caucasian populations.

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Section: Discussionsupporting

confidence: 43%

“…[1][2][3] At least two loci on the X chromosome can mutate to cause retinitis pigmentosa (RP). The first, RP2 (type 2), was recently identified by positional cloning in Xp11.3.…”

Section: Introductionmentioning

confidence: 44%

Mutation analysis of the RPGR gene reveals novel mutations in south European patients with X-linked retinitis pigmentosa

et al. 1999

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“…XLRP is considered clinically severe, with early onset and rapid progression, often leading to severe visual handicap before the fourth decade [Bird, 1975;Fishman et al, 1988]. A milder phenotype is often present in female carriers, probably due to random X-inactivation.…”

Section: Introductionsupporting

confidence: 42%

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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“…It is inherited in autosomal recessive, autosomal dominant as well as X-linked manner. Patients exhibit symptoms of night blindness and loss of peripheral vision (due to rod death) in the first two decades of life, which is followed by complete blindness due to loss of cone photoreceptors [54][55]. Loss of cones can either be due to the fact that the causative gene is also expressed in cone photoreceptors or due to starvation or loss of availability of trophic factors secreted from the rods (majority cell type in photoreceptor layer; 95-97%) if the mutation is in a rod-specific gene [56][57].…”

Section: Non-syndromic Retinal Ciliopathiesmentioning

confidence: 48%