Current mutation discovery approaches in Retinitis Pigmentosa
Current mutation discovery approaches in Retinitis Pigmentosa
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DOI：
10.1016/j.visres.2012.09.012
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发表时间：
2012-12-15
期刊：
影响因子：
1.8
通讯作者：
Ruiz-Ederra, Javier
中科院分区：
文献类型：
--
作者：
Anasagasti, Ander;Irigoyen, Cristina;Ruiz-Ederra, Javier
视网膜色素变性是遗传性视网膜变性中最常见的一种，在全球范围内约为1/3500-5000。这是一组由基因决定的视网膜疾病，由于视杆细胞和视锥细胞感受器受损而导致进行性视力丧失。RP可遗传为常染色体隐性、常染色体显性或X连锁性状。非孟德尔遗传模式，如双基因、母体(线粒体)或复合杂合性也有报道。到目前为止，已有超过65个基因与综合征和非综合征形式的RP有关，仅占所有RP病例的60%左右。由于遗传模式的高度异质性和多样性，综合征性和非综合征性RP的分子诊断非常具有挑战性，全世界40%的RP病例的遗传性尚不清楚。然而，在人类基因组计划的推动下，新的测序方法导致测序成本指数直线下降，从而使在未来几年内将RP患者的分子检测纳入常规临床实践是可行的。在这里，我们总结了目前应用最广泛的最先进的技术应用于RP的分子诊断，并阐述了它们在这种复杂遗传病的分子诊断中的优势和劣势。(C)2012爱思唯尔有限公司。保留所有权利。
With a worldwide prevalence of about 1 in 3500-5000 individuals, Retinitis Pigmentosa (RP) is the most common form of hereditary retinal degeneration. It is an extremely heterogeneous group of genetically determined retinal diseases leading to progressive loss of vision due to impairment of rod and cone photoreceptors. RP can be inherited as an autosomal-recessive, autosomal-dominant, or X-linked trait. Non-Mendelian inheritance patterns such as digenic, maternal (mitochondrial) or compound heterozygosity have also been reported. To date, more than 65 genes have been implicated in syndromic and non-syndromic forms of RP, which account for only about 60% of all RP cases. Due to this high heterogeneity and diversity of inheritance patterns, the molecular diagnosis of syndromic and non-syndromic RP is very challenging, and the heritability of 40% of total RP cases worldwide remains unknown. However new sequencing methodologies, boosted by the human genome project, have contributed to exponential plummeting in sequencing costs, thereby making it feasible to include molecular testing for RP patients in routine clinical practice within the coming years. Here, we summarize the most widely used state-of-the-art technologies currently applied for the molecular diagnosis of RP, and address their strengths and weaknesses for the molecular diagnosis of such a complex genetic disease. (C) 2012 Elsevier Ltd. All rights reserved.