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Retinitis pigmentosa.Orphanet
J Rare Dis. 2006 Oct 11;1:40
ABSTRACT:
Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by
the loss of photoreceptors and characterized by retinal pigment
deposits visible on fundus examination. Prevalence of non syndromic RP
is approximately 1/4,000. The most common form of RP is a rod-cone
dystrophy, in which the first symptom is night blindness, followed by
the progressive loss in the peripheral visual field in daylight, and
eventually leading to blindness after several decades. Some extreme
cases may have a rapid evolution over two decades or a slow
progression that never leads to blindness. In some cases, the clinical
presentation is a cone-rod dystrophy, in which the decrease in visual
acuity predominates over the visual field loss. RP is usually non
syndromic but there are also many syndromic forms, the most frequent
being Usher syndrome. To date, 45 causative genes/loci have been
identified in non syndromic RP (for the autosomal dominant, autosomal
recessive, X-linked, and digenic forms). Clinical diagnosis is based
on the presence of night blindness and peripheral visual field
defects, lesions in the fundus, hypovolted electroretinogram traces,
and progressive worsening of these signs. Molecular diagnosis can be
made for some genes, but is not usually performed due to the
tremendous genetic heterogeneity of the disease. Genetic counseling is
always advised. Currently, there is no therapy that stops the
evolution of the disease or restores the vision, so the visual
prognosis is poor. The therapeutic approach is restricted to slowing
down the degenerative process by sunlight protection and
vitaminotherapy, treating the complications (cataract and macular
edema), and helping patients to cope with the social and psychological
impact of blindness. However, new therapeutic strategies are emerging
from intensive research (gene therapy, neuroprotection, retinal
prosthesis).
Retinitis
pigmentosa, pigmentary retinopathies, and neurologic diseases.Curr
Neurol Neurosci Rep. 2006 Sep;6(5):403-13
Retinitis
pigmentosa (RP) refers to a group of inherited retinal diseases with
phenotypic and genetic heterogeneity. The pathophysiologic basis of
the progressive visual loss in patients with RP is not completely
understood but is felt to be due to a primary retinal photoreceptor
cell degenerative process mainly affecting the rods of the peripheral
retina. In most cases RP is seen in isolation (nonsyndromic), but in
some other cases it may be a part of a genetic, metabolic, or
neurologic syndrome or disorder. Nyctalopia, or night blindness, is
the most common symptom of RP. The classic fundus appearance of RP
includes retinal pigment epithelial cell changes resulting in retinal
hypo- or hyperpigmentation ("salt-and-pepper"), retinal granularity,
and bone spicule formation. The retinal vessels are often narrowed or
attenuated and there is a waxy pallor appearance of the optic nerve
head. Electroretinography will demonstrate rod and cone photoreceptor
cell dysfunction and is a helpful test in the diagnosis and monitoring
of patients with RP. A detailed history with pedigree analysis, a
complete ocular examination, and the appropriate paraclinical testing
should be performed in patients complaining of visual difficulties at
night or in dim light. This review discusses the clinical
manifestations of RP as well as describing the various systemic
diseases, with a special emphasis on neurologic diseases, associated
with a pigmentary retinopathy.
Light in
retinitis pigmentosa.Trends
Genet. 2005 Feb;21(2):103-10.
Retinitis
pigmentosa (RP) is one of the most genetically heterogeneous inherited
disorders. Twelve genes have now been identified in the autosomal
dominant form of the disease, including some recently characterized
genes that show unprecedented and fascinating traits in both their
function and in their expression profiles. These include many widely
expressed genes encoding components of the spliceosome and a guanine
nucleotide synthesis gene. Intriguingly, the most recently identified
dominant gene does not appear to be expressed in the neuronal retina
but is expressed in the capillaries of the choroid. In attempting to
understand the effects of mutations in these genes, investigators are
forced to re-evaluate their thinking on the molecular mechanisms of
genetic blindness and to undertake an increasingly inter-disciplinary
approach in their analysis of this disease. Recently, this has
resulted in significant developments in the elucidation of the
molecular pathogenesis of RP.
Gene mutations
in retinitis pigmentosa and their clinical implications.Clin
Chim Acta. 2005 Jan;351(1-2):5-16
Retinitis
pigmentosa (RP) is a group of inherited progressive retinal diseases
affecting about 1 in 3500 people worldwide. So far, there is no
prevention or cure, with permanent visual loss or even blindness the
ultimate consequence usually after midlife. The genetics of RP are
complex. It can be sporadic, autosomal dominant, autosomal recessive,
or X-linked. Thirty-two genes are known to be associated with RP,
sometimes the same gene gets involved in different inheritance traits.
Some RP cases have a digenic cause. About 60% RP cases still have no
known genetic cause. A large number of mutations cause RP, and they
can be deletions, insertions, or substitutions that cause missense
mutations or truncations. The RHO, RP1, and RPGR genes contribute the
greatest number of known mutations causative of RP. But there is no
single mutation that alone accounts for more than 10% of unrelated
patients. Genetic testing for RP therefore requires screening for a
group of genes. High-throughput and automated sequence detection
technologies are essential. Due to the complexity in phenotype and
genetics, and the fact that RP is untreatable, genetic testing for
presymptomatic diagnosis of RP is controversial. Meanwhile, new genes
are still to be identified, mostly by family linkage and sib-pair
analysis. Research on gene therapy for RP requires information on gene
mutations causative of RP.
Histopathologic study of variation in severity of retinitis pigmentosa
due to the dominant rhodopsin mutation Pro23His.
Am J Ophthalmol.
2002 Aug;134(2):290-3.
PURPOSE: To
compare histopathologic findings in an autopsy eye of an 87-year-old
woman with retinitis pigmentosa and the rhodopsin mutation Pro23His
with findings in an autopsy eye of a 77-year-old female relative
(first cousin) with retinitis pigmentosa and the same mutation.
DESIGN: Histopathologic study. METHODS: One eye from each patient was
prepared for light and electron microscopy within 5 hours after death.
Photoreceptor nuclear counts were performed. RESULTS: Photoreceptor
degeneration and intraretinal bone spicule pigmentation were evident
in both cases. The younger patient had more extensive photoreceptor
loss and more intraretinal pigmentation than her older relative.
CONCLUSION: A marked variation in the extent of retinal degeneration
can be seen in two relatives with retinitis pigmentosa and rhodopsin,
Pro23His. This study supports the idea that factors other than the
primary gene defect are responsible for the severity of this
condition.
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