中国北京视网膜母细胞瘤患儿的RB1突变谱及遗传管理咨询
The RB1 Mutation Spectrum and Genetic Management Consultation in Pediatric Patients with Retinoblastoma in Beijing, China.
作者信息
Xie Ying, Xu Xiao-Lin, Wei Wen-Bin
机构信息
Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophthalmology and Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People's Republic of China.
Department of Opthalmology, Shanxi Provincial People's Hospital, Taiyuan, 030012, People's Republic of China.
出版信息
Risk Manag Healthc Policy. 2021 Aug 21;14:3453-3463. doi: 10.2147/RMHP.S322373. eCollection 2021.
OBJECTIVE
The present study screened the structural mutations of the retinoblastoma (RB1) gene using gene capture and a preliminary exploration of the correlation between the genotypes and phenotypes.
METHODS
A total of 45 formalin-fixed paraffin-embedded (FFPE) tissue samples and 12 peripheral venous blood samples from patients with retinoblastoma (RB) confirmed by pathological examination at Beijing Tongren Hospital were collected between May 2019 and May 2021. DNA from the samples was extracted, sequenced, and analyzed to detect the mutations in the RB1 gene by designing the targeted capture probes for exons and the flanking sequences of the gene.
RESULTS
Of the 45 FFPE tissue samples, 23 were from male patients and 22 were from female patients, all aged between 4 months and 10 years, with an average age of 2.5 ± 1.3 years. Two of these patients had bilateral RB and 43 had unilateral RB (23 in the right eye and 20 in the left eye). Of the 12 peripheral venous blood samples, 7 were from male patients and 5 were from female patients, all aged between 8 months and 4 years, with an average age of 1.3 ± 0.9 years. Two of these patients had bilateral RB and 10 had unilateral RB (8 in the right eye and 2 in the left eye). Three de novo pathogenic mutations were found in the FFPE tissues, along with one de novo potentially pathogenic mutation, while three de novo potentially pathogenic mutations were found in the blood samples.
CONCLUSION
Gene capture is a low-cost and efficient method for the gene sequencing of RB. A total of seven de novo mutations were identified through mutation testing of the pathogenic gene RB1 in 56 pediatric patients with RB. This complemented the mutation spectrum of the RB1 gene and helped to improve the molecular diagnosis of RB, thereby providing a basis for genetic counseling and prediction of the clinical phenotype, as well as for the genetic testing of the offspring of patients with RB.
CLINICAL REGISTRATION NUMBER
ChiCTR-EPC-17013892.
目的
本研究采用基因捕获技术筛查视网膜母细胞瘤（RB1）基因的结构突变，并初步探索基因型与表型之间的相关性。
方法
于2019年5月至2021年5月期间，收集了北京同仁医院经病理检查确诊为视网膜母细胞瘤（RB）患者的45份福尔马林固定石蜡包埋（FFPE）组织样本和12份外周静脉血样本。提取样本中的DNA，进行测序和分析，通过设计针对该基因外显子及其侧翼序列的靶向捕获探针，检测RB1基因中的突变。
结果
45份FFPE组织样本中，男性患者23例，女性患者22例，年龄均在4个月至10岁之间，平均年龄为2.5±1.3岁。其中2例患者为双侧RB，43例为单侧RB（右眼23例，左眼20例）。12份外周静脉血样本中，男性患者7例，女性患者5例，年龄均在8个月至4岁之间，平均年龄为1.3±0.9岁。其中2例患者为双侧RB，10例为单侧RB（右眼8例，左眼2例）。在FFPE组织中发现了3个新发致病突变以及1个新发潜在致病突变，在血样中发现了3个新发潜在致病突变。
结论
基因捕获是一种用于RB基因测序的低成本、高效方法。通过对56例小儿RB患者的致病基因RB1进行突变检测，共鉴定出7个新发突变。这补充了RB1基因的突变谱，有助于提高RB的分子诊断水平，从而为遗传咨询、临床表型预测以及RB患者后代的基因检测提供依据。
临床注册号
ChiCTR-EPC-17013892。
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