Pigmented paravenous chorioretinal atrophy is associated with a mutation within the crumbs homolog 1 (CRB1) gene.

Ophthalmic Research Centre, Institute of Clinical Science, Queen's University of Belfast, Belfast, Northern Ireland, United Kingdom.
Investigative Ophthalmology &amp Visual Science (Impact Factor: 3.66). 02/2005; 46(1):322-8. DOI: 10.1167/iovs.04-0734
Source: PubMed

ABSTRACT Pigmented paravenous chorioretinal atrophy (PPCRA) is an unusual retinal degeneration characterized by accumulation of pigmentation along retinal veins. The purpose of this study was to describe the phenotype of a family with PPCRA, determine the mode of inheritance, and identify the causal mutation.
Ophthalmic examination was performed on seven family members and serially detailed in the proband over a 3-year period. Blood samples were collected and DNA extracted. All 12 coding exons and the 5' promoter region of the crumbs homologue 1 (CRB1) gene were PCR amplified and DNA sequenced. In silico homology modeling was performed on the mutated protein domain.
Subtle symmetrical chorioretinal atrophy in the inferior quadrant was the earliest clinical sign detectable within this family. Paravenous pigmentation occurred initially in the far periphery, progressing centrally, with atrophy later becoming more widespread, involving the nasal, then the temporal, and finally the upper quadrant. A novel, dominant Val162Met mutation within the fourth EGF-like domain of CRB1 cosegregates with the PPCRA phenotype. It is thought to affect domain structure, because codon 162 is involved in hydrogen bonding between the antiparallel beta-strands of the major beta-sheet, causing sufficient perturbation of the backbone that the domain-stabilizing hydrogen bond does not form or is weakened.
PPCRA was dominantly inherited in this family, but exhibited variable expressivity. Males are more likely to exhibit a severe phenotype, whereas females may remain virtually asymptomatic even in later years. The PPCRA phenotype is associated with a Val162Met mutation in CRB1 which is likely to affect the structure of the CRB1 protein.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Leber congenital amaurosis (LCA) is a hereditary condition involving severe visual loss or blindness that develops within the first year of life. LCA occurs as syndromic and nonsyndromic forms, and is mostly of autosomal-recessive inheritance. To date, mutations in 19 genes are known to be associated with nonsyndromic LCA phenotypes. Mutations in all known genes account for disease in 70% or less of LCA patients, suggesting that unidentified genes are responsible in the remaining cases. High-throughput screening methods such as mutation chips and exome sequencing have accelerated the pace of genetic discovery in LCA. Genetic testing is useful in counseling families and in confirming diagnosis in ambiguous cases. Gene-based therapy with the RPE65 gene has completed the first phase of clinical trials and shows promising results. Various other gene-specific and other modes of therapy are in experimental stages and are expected to progress to human trials in the near future.
    Expert Review of Ophthalmology 01/2014; 7(2). DOI:10.1586/eop.12.14
  • [Show abstract] [Hide abstract]
    ABSTRACT: Inherited retinal diseases are uncommon pathologies and one of the most harmful causes of childhood and adult blindness. Leber congenital amaurosis (LCA) is the most severe kind of these diseases accounting for approximately 5% of the whole retinal dystrophies and 20% of the children that study on blind schools. Clinical ophthalmologic findings including severe vision loss, nystagmus and ERG abnormalities should be suspected through the first year of life in this group of patients. Phenotypic variability is found when LCA patients have a full ophthalmologic examination. However, a correct diagnosis may be carried out; the determination of ophthalmologic clues as light sensibility, night blindness, fundus pigmentation, among other, join with electroretinographics findings, optical coherence tomography, and new technologies as molecular gene testing may help to reach to a precise diagnosis. Several retinal clinical features in LCA may suggest a genetic or gene particular defect; thus genetic-molecular tools could directly corroborate the clinical diagnosis. Currently, approximately 20 genes have been associated to LCA. In this review, historical perspective, clinical ophthalmological findings, new molecular-genetics technologies, possible phenotype-genotypes correlations, and gene therapy for some LCA genes are described.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pigmented paravenous retinochoroidal atrophy (PPRCA) is an uncommon disease characterized by perivenous aggregations of pigment clumps associated with peripapillary and radial zones of retinochoroidal atrophy that are distributed along the retinal veins. Patients are usually asymptomatic and the disease process is non-progressive or slow and subtly progressive. It is commonly bilateral and symmetric. The cause of the condition may be unknown or idiopathic, although a dysgenetic, degenerative, hereditary etiology or even an inflammatory cause has been hypothesized. A non-inflammatory cause is referred to as primary, while inflammation-associated PPRCA is referred to as secondary or pseudo PPRCA. The present study reviewed and summarized the features of PPRCA.
    Experimental and therapeutic medicine 06/2014; 7(6):1439-1445. DOI:10.3892/etm.2014.1648 · 0.94 Impact Factor

Full-text (2 Sources)

Available from
Jun 2, 2014