目的:本研究旨在探索可能导致视网膜外插管(ORT)的遗传变异,估计这些候选基因中ORT的患病率,并探讨遗传性视网膜疾病(IRD)患者ORT的临床病因,关于每个基因。
方法:回顾性队列研究。
方法:对565例分子诊断为IRD的患者进行了回顾性横断面审查,确认每个患者各自谱域光学相干断层扫描(SD-OCT)成像中所记录的ORT的存在。使用SD-OCT成像,分析了ORT的存在与特定遗传变异和表型特征的关系.结果包括在两个基因特异性队列中观察到的ORT频率:非视网膜色素上皮(RPE)特异性基因,和RPE特异性基因;并研究由这些基因中的变异引起的类似特征。
结果:在纳入本研究的565名患者中,104在SD-OCT上显示ORT。我们观察到来自我们患者队列的以下基因中的ORT频率:100%(23/23)对于CHM,100%(2/2)用于PNPLA6,100%(4/4)用于RCBTB1,100%formtDNA[100%(4/4)用于MT-TL1和100%(1/1)formtDNA缺失],100%(1/1)对于OAT,95.2%(20/21)用于CYP4V2,72.7%(8/11)用于女性携带者,C1QTNF5占66.7%(2/3),PROM1占57.1%(8/14),PRPH2占53.8%(7/13),CERKL占42.9%(3/7),28.6%(2/7)用于CDHR1,20%(1/5)用于RPE65,4%(18/445)用于ABCA4。相比之下,在任何具有光感受器特异性基因变异的患者中均未观察到ORT,如RHO(n=13),USH2A(n=118),EYS(n=70),PDE6B(n=10),PDE6A(n=4),和其他人。
结论:这些结果说明了由RPE特异性基因变异引起的ORT和IRD的存在之间的令人信服的关联。以及非RPE特异性基因。相比之下,由光感受器特异性基因引起的IRD通常与ORT发生无关。进一步的分析表明,ORT倾向于在具有较温和的体内色素迁移(IPM)的IRD中表现出来,这一发现通常与RPE特异性基因相关。这些关于ORT的发现,遗传因素,眼底的萎缩模式,IPM为IRD的复杂病因提供了有价值的见解。未来的前瞻性研究需要进一步探索这些背景下ORT的关联和潜在机制。
OBJECTIVE: This study aims to explore genetic variants that potentially lead to outer retinal tubulation (ORT), estimate the prevalence of ORT in these candidate genes, and investigate the clinical etiology of ORT in patients with inherited retinal diseases (IRDs), with respect to each gene.
METHODS: Retrospective cohort study.
METHODS: A retrospective cross-sectional review was conducted on 565 patients with molecular diagnoses of IRD, confirming the presence of ORT as noted in each patient\'s respective spectral-domain optical coherence tomography (SD-OCT) imaging. Using SD-OCT imaging, the presence of ORT was analyzed in relation to specific genetic variants and phenotypic characteristics. Outcomes included the observed ORT frequencies across two gene-specific cohorts: non- retinal pigment epithelium (RPE)-specific genes, and RPE-specific genes; and to investigate the analogous characteristics caused by variants in these genes.
RESULTS: Among the 565 patients included in this study, 104 exhibited ORT on SD-OCT. We observed ORT frequencies among the following genes from our patient cohort: 100% (23/23) forCHM, 100%(2/2) forPNPLA6, 100% (4/4) forRCBTB1, 100% formtDNA[100% (4/4) forMT-TL1and 100% (1/1) formtDNAdeletion], 100% (1/1) forOAT, 95.2% (20/21) forCYP4V2, 72.7% (8/11) forCHMfemale carriers, 66.7% (2/3) forC1QTNF5, 57.1% (8/14) forPROM1, 53.8% (7/13) forPRPH2, 42.9% (3/7) forCERKL, 28.6% (2/7) forCDHR1, 20% (1/5) forRPE65, 4% (18/445) forABCA4.In contrast, ORT was not observed in any patients with photoreceptor-specific gene variants, such asRHO(n=13),USH2A(n=118),EYS(n=70),PDE6B(n=10),PDE6A(n=4),and others.
CONCLUSIONS: These results illustrate a compelling association between the presence of ORT and IRDs caused by variants in RPE-specific genes, as well as non-RPE-specific genes. In contrast, IRDs caused by photoreceptor-specific genes are typically not associated with ORT occurrence. Further analysis revealed that ORT tends to manifest in IRDs with milder intraretinal pigment migration (IPM), a finding that is typically associated with RPE-specific genes. These findings regarding ORT, genetic factors, atrophic patterns in the fundus, and IPM provide valuable insight into the complex etiology of IRDs. Future prospective studies are needed to further explore the association and underlying mechanisms of ORT in these contexts.