基于下一代目标区域序列捕获测序技术的MEN2早期个体化诊疗策略研究

通过整合家系调查、基于下一代目标区域捕获测序技术（T-NGS）的RET基因全外显子区域（突变/SNPs）测序和术前降钙素水平等，①勾勒国人RET突变基因型-MEN2表型的关系谱，分析RET基因SNPs在国人MEN 2差异表型中的可能修饰作用；②评估T-NGS检测RET基因的准确性和实用性，为其直接应用于无同源重复序列的单基因遗传病的临床检测提供依据。③探讨国人MEN2的预防性甲状腺切除术的手术时机、手术方式和范围，以及MEN2-PHEO的保留肾上腺皮质功能的肾上腺切除术的运用评估。④初步勾勒国人MEN2的早期诊疗策略规范，推动实施精细化和个体化的诊疗，减少或避免MEN2的临床危害及其术后并发症，最大限度地提高MEN2无病生存率，为最终建立集MEN2的预防、预警和早期诊疗、晚期补救为一体的国人个体化MEN2诊疗平台体系，促进国人MEN2诊治水平的整体提高。

By integrating pedigrees, analysis of preoperative calcitonin levels, and then screening of RET protein-coding region (mutations/SNPs) based on targeted next-generation sequencing (T-NGS), we aim to (1) generalize the relationship between genotype and phenotype in Chinese multiple endocrine neoplasia type 2 (MEN2)-related RET mutations and/or SNPs; (2) assess the accuracy and feasibility of RET screening by targeted next-generation sequencing, which could be a model for genetic diagnosis in other monogenic diseases with multiple exons and without homologous repetitive sequence within their causative genes; (3) demonstrate the time course, surgical procedures and extent of prophylactic thyroidectomy for Chinese MEN2 patients, and evaluate the utility of cortical sparing surgery for MEN2-related phaeochromocytoma; (4) attempt to establish an refinement and individualized strategy of prevention, early diagnosis and late remedy treatment for Chinese MEN2 patients, to reduce clinic hazards and postoperative complications，improve disease-free survival and promote the overall improvement of the diagnosis and treatment.