Li Feng, Chen Weiying, Chen Zhenyu, Lian Bijun, Fang Xudong, Jin Hangyang, Wang Huihong, Zhao Jianqiang, Zhang Yiming, Qi Xiaoping
Department of Oncologic and Urologic Surgery, The 903rd PLA Hospital, Hangzhou Medical College, Hangzhou, Zhejiang Province, China.
Department of Urology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Enze Hospital of Hangzhou Medical College, Taizhou Enze Medical Center (Group), Taizhou, Zhejiang Province, China.
PLoS One. 2025 Sep 11;20(9):e0332136. doi: 10.1371/journal.pone.0332136. eCollection 2025.
To investigate the genotype-phenotype correlations of multiple endocrine neoplasia type 2A (MEN2A) caused by mutations in exon 10 of the RET gene in Ethnic Han Chinese.
A retrospective analysis was conducted on the family history and genetic characteristics of 14 independent MEN2A pedigrees, all carrying exon 10 mutations of the RET gene, from July 2003 to August 2023.
A total of 74 out of 133 participants carried germline mutations in exon 10 of the RET gene. The cohort included 26 males and 48 females, with nine types of mutations observed: p.C609R, p.C611F/Y, p.C618G/R/S/Y and p.C620R/S. Of these, the C618 mutation was the most prevalent (71.6%), followed by p.C611 (22.9%), p.C620 (4.1%), and p.C609 (1.4%). The penetrance rates for medullary thyroid carcinoma (MTC), pheochromocytoma, hyperparathyroidism, hirschsprung disease, and cutaneous lichen amyloidosis were 90.3%, 6.9%, 2.8%, 1.4% and 1.4%, respectively. Among the 72 patients with available clinical information, 41 (56.9%) exhibited symptoms of MTC. Comparison of the age at diagnosis, size of MTC, and the positive rate of cervical lymph node metastasis (N1) revealed significant differences between patients with symptomatic and asymptomatic MTC (all P < 0.05). There was a significant difference in the positivity rate of N1 between patients with the p.C618/C620 mutations and those with the p.C609/C611 mutations. Additionally, there was a significant difference in the initial serum calcitonin levels between N1 and N0 patients (P < 0.05).
Exon 10 mutations of the RET gene are frequently located in codon 618 and contribute to the familial MTC phenotype. To improve the recognition of MEN2A, integrating family history, testing for RET mutations, and monitoring serum calcitonin levels are essential for early diagnosis and personalised treatment.
探讨汉族人群中由RET基因第10外显子突变引起的2A型多发性内分泌腺瘤病（MEN2A）的基因型与表型的相关性。
对2003年7月至2023年8月期间14个独立的MEN2A家系进行回顾性分析，所有家系均携带RET基因第10外显子突变，分析其家族史和遗传特征。
133名参与者中共有74人携带RET基因第10外显子的种系突变。该队列包括26名男性和48名女性，观察到9种突变类型：p.C609R、p.C611F/Y、p.C618G/R/S/Y和p.C620R/S。其中，C618突变最为常见（71.6%），其次是p.C611（22.9%）、p.C620（4.1%）和p.C609（1.4%）。甲状腺髓样癌（MTC）、嗜铬细胞瘤、甲状旁腺功能亢进、先天性巨结肠和皮肤苔藓样淀粉样变的外显率分别为90.3%、6.9%、2.8%、1.4%和1.4%。在72例有可用临床信息的患者中，41例（56.9%）表现出MTC症状。有症状和无症状MTC患者在诊断年龄、MTC大小和颈部淋巴结转移阳性率（N1）方面的比较显示出显著差异（所有P < 0.05）。p.C618/C620突变患者与p.C609/C611突变患者的N1阳性率存在显著差异。此外，N1和N0患者的初始血清降钙素水平存在显著差异（P < 0.05）。
RET基因第10外显子突变常位于密码子618，与家族性MTC表型相关。为提高对MEN2A的认识，综合家族史、RET突变检测和监测血清降钙素水平对于早期诊断和个性化治疗至关重要。
