METHODS: We assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, newly analysed), including Usher syndrome, Leber congenital amaurosis and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines.
RESULTS: A total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 patients with RP. This led to a genetic diagnostic rate in 38.6% of patients with RP, with EYS accounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for patients with CRD was 28.2%, with RP-related genes significantly contributing over other allied diseases.
CONCLUSIONS: A large-scale genetic analysis using the J-IRD-VI guidelines highlighted the population-specific genetic findings for Japanese patients with IRD; these findings serve as a foundation for the clinical application of gene-specific therapies.
方法:我们评估了2325名先证者的RP(n=2155,包括以前用相同测序组测序的n=1204)和相关疾病(n=170,新分析),包括Usher综合征,Leber先天性黑蒙和锥棒营养不良(CRD)。使用一组86个基因进行靶测序。根据J-IRD-VI指南解释变体。
结果:共检测到3564个变异,其中524个变体被解释为致病性或可能致病性。在这524个变体中,在我们对1204例RP患者的早期研究中,有280例(53.4%)未被发现或被解释为未知意义的变体或良性变体。这导致38.6%的RP患者的遗传诊断率,EYS占基因解决患者的46.7%,与我们之前的研究相比,诊断率提高了9%。CRD患者的基因诊断率为28.2%,与RP相关的基因对其他相关疾病有重要贡献。
结论:使用J-IRD-VI指南的大规模遗传分析强调了日本IRD患者的群体特异性遗传发现;这些发现为基因特异性疗法的临床应用奠定了基础。