Genes and mutations causing retinitis pigmentosa. Clin Genet

Department of Ophthalmology and Visual Science, School of Medicine, The University of Texas Health Science Center, Houston, TX 77030, USA.
Archives of Ophthalmology (Impact Factor: 4.4). 03/2007; 125(2):151-8. DOI: 10.1001/archopht.125.2.151
Source: PubMed


Exceptional progress has been made during the past two decades in identifying genes causing inherited retinal diseases such as retinitis pigmentosa. An inescapable consequence is that the relationship between genes, mutations, and clinical findings has become very complex. Success in identifying the causes of inherited retinal diseases has many implications, including a better understanding of the biological basis of vision and insights into the processes involved in retinal pathology. From a clinical point of view, there are two important questions arising from these developments: where do we stand today in finding disease-causing mutations in affected individuals, and what are the implications of this information for clinical practice? This perspective addresses these questions specifically for retinitis pigmentosa, but the observations apply generally to other forms of inherited eye disease.

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Available from: Lori S Sullivan,
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    • "Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophies (IRD) and is clinically and genetically heterogeneous. At least 50 genes have been identified for nonsyndromic RP [1] (RetNet; provided in the public domain by the University of Texas Houston Health Science Center, Houston, TX). "
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    ABSTRACT: The aim of this study was to gain information about disease prevalence and to identify the responsible genes for inherited retinal dystrophies (IRD) in Japanese populations. Clinical and molecular evaluations were performed on 349 patients with IRD. For segregation analyses, 63 of their family members were employed. Bioinformatics data from 1,208 Japanese individuals were used as controls. Molecular diagnosis was obtained by direct sequencing in a stepwise fashion utilizing one or two panels of 15 and 27 genes for retinitis pigmentosa patients. If a specific clinical diagnosis was suspected, direct sequencing of disease-specific genes, that is, ABCA4 for Stargardt disease, was conducted. Limited availability of intrafamily information and decreasing family size hampered identifying inherited patterns. Differential disease profiles with lower prevalence of Stargardt disease from European and North American populations were obtained. We found 205 sequence variants in 159 of 349 probands with an identification rate of 45.6%. This study found 43 novel sequence variants. In silico analysis suggests that 20 of 25 novel missense variants are pathogenic. EYS mutations had the highest prevalence at 23.5%. c.4957_4958insA and c.8868C>A were the two major EYS mutations identified in this cohort. EYS mutations are the most prevalent among Japanese patients with IRD.
    Journal of Ophthalmology 07/2015; 2015:819760. DOI:10.1155/2015/819760 · 1.43 Impact Factor
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    • "rhodopsin in first place, but also phosphodiesterase etc.), transcription factors (i.e. Crx, Nrl), disc membrane-associated glycoproteins (peripherin), ionic channels (the light sensitive cationic channel), structural proteins of the cilium etc. (Daiger et al., 2013; Roesch et al., 2012). The biological mechanisms linking the primary mutation responsible for RP and rod damage remain still elusive. "
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    ABSTRACT: Retinal photoreceptors are highly specialized and performing neurons. Their cellular architecture is exquisitely designed to host a high concentration of molecules involved in light capture, phototransduction, electric and chemical signaling, membrane and molecular turnover, light and dark adaption, network activities etc. Such high efficiency and molecular complexity require a great metabolic demand, altogether conferring to photoreceptors particular susceptibility to external and internal insults, whose occurrence usually precipitate into degeneration of these cells and blindness. In Retinitis Pigmentosa, an impressive number of mutations in genes expressed in the retina and coding for a large varieties of proteins leads to the progressive death of photoreceptors and blindness. Recent advances in molecular tools have greatly facilitated the identification of the underlying genetics and molecular bases of RP leading to the successful implementation of gene therapy for some types of mutations, with visual restoration in human patients. Yet, genetic heterogeneity of RP makes mutation-independent approaches highly desirable, although many obstacles pave the way to general strategies for treating this complex disease, which remains orphan. The review will focus on treatments for RP based on pharmacological tools, choosing, among the many ongoing studies, approaches which rely on strong experimental evidence or rationale. For perspective treatments, new concepts are foreseen to emerge from basic studies elucidating the pathways connecting the primary mutations to photoreceptor death, possibly revealing common molecular targets for drug intervention. Copyright © 2015. Published by Elsevier Ltd.
    Progress in Retinal and Eye Research 06/2015; 48. DOI:10.1016/j.preteyeres.2015.06.005 · 8.73 Impact Factor
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    • "These neurons discern dim light (scotopic vision) and are very sensitive to light within the maximum absorption spectra of their visual pigment, rhodopsin [23]. Rod degeneration in the first phase of RP is triggered by mutations in more than 50 different genes [24] and results in an increase in oxygen tension, which in turn affects the cones [25] [26]. Taken together, these results suggest that RdCVFL is involved in the defense mechanism against light-induced oxidative injury on photoreceptors , rods, and cones, while RdCVF protects cones. "

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