Unravelling the genetic basis of simplex Retinitis Pigmentosa cases
Unravelling the genetic basis of simplex Retinitis Pigmentosa cases
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DOI：
10.1038/srep41937
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发表时间：
2017-02-03
影响因子：
4.6
通讯作者：
Antinolo, Guillermo
中科院分区：
文献类型：
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作者：
Bravo-Gil, Nereida;Gonzalez-del Pozo, Maria;Antinolo, Guillermo
色素性视网膜炎（RP）是遗传性视网膜营养不良（IRD）的最常见形式，其最终特征在于光感受器变性。RP表现出巨大的临床和遗传异质性，可以作为常染色体显性（ad）、常染色体隐性（ar）和X连锁（xl）疾病遗传。虽然每种形式的相对患病率在人群之间有所不同，但大部分患者（西班牙为41%）代表单纯病例（sRP），其中遗传方式未知。分子遗传学诊断对于sRP患者至关重要，但也具有挑战性，因为迄今为止鉴定的81个RP基因中的任何一个都可能是致病基因。在此，我们报告了使用定制的靶向基因面板组成的68 IRD基因的分子表征的106 sRP的情况下。诊断率为62.26%（106例中的66例），临床细化比例为30.3%，表明即使对于临床不明确的病例，这种基因组方法也具有高效率。这里诊断出的大量患者使我们能够详细研究sRP的遗传基础。已解决的sRP队列由62.1%的arRP病例、24.2%的adRP病例和13.6%的xlRP病例组成，这意味着对患者和家属进行咨询的结果。
Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy (IRD) characterized ultimately by photoreceptors degeneration. Exhibiting great clinical and genetic heterogeneity, RP can be inherited as an autosomal dominant (ad), autosomal recessive (ar) and X-linked (xl) disorder. Although the relative prevalence of each form varies somewhat between populations, a major proportion (41% in Spain) of patients represent simplex cases (sRP) in which the mode of inheritance is unknown. Molecular genetic diagnostic is crucial, but also challenging, for sRP patients because any of the 81 RP genes identified to date may be causative. Herein, we report the use of a customized targeted gene panel consisting of 68 IRD genes for the molecular characterization of 106 sRP cases. The diagnostic rate was 62.26% (66 of 106) with a proportion of clinical refinements of 30.3%, demonstrating the high efficiency of this genomic approach even for clinically ambiguous cases. The high number of patients diagnosed here has allowed us to study in detail the genetic basis of the sRP. The solved sRP cohort is composed of 62.1% of arRP cases, 24.2% of adRP and 13.6% of xlRP, which implies consequences for counselling of patients and families.