遗传性嗜铬细胞瘤/副神经节瘤及其相关综合征的临床与遗传学研究

唐朋; 兰卫华; 张尧; 张军; 舒泽华; 李珂; 黄灶明; 黄义强; 刘秋礼; 江军

doi:10.16016/j.2097-0927.202302129

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遗传性嗜铬细胞瘤/副神经节瘤及其相关综合征的临床与遗传学研究

临床医学 | 更新时间：2026-01-09

- 遗传性嗜铬细胞瘤/副神经节瘤及其相关综合征的临床与遗传学研究
- Hereditary pheochromocytoma/paraganglioma and associated syndromes: a clinical and genetic study
- 陆军军医大学学报 2024年46卷第4期页码：377-383
- 作者机构：
  
  400042 重庆，陆军特色医学中心泌尿外科
- 作者简介：
  
  [江军，E-mail：jiangjun_64@163.comJIANG Jun, E-mail: jiangjun_64@163.com
- 基金信息：
  
  陆军军医大学临床医学科研人才培养计划(2018XLC3073)
- DOI：10.16016/j.2097-0927.202302129
  中图分类号： R195.4;R394.1;R736.6
- 收稿：2023-02-23，
  
  修回：2023-09-11，
  
  纸质出版：2024-02-28
- 稿件说明：
移动端阅览
唐朋, 兰卫华, 张尧, 等. 遗传性嗜铬细胞瘤/副神经节瘤及其相关综合征的临床与遗传学研究[J]. 陆军军医大学学报, 2024,46(4):377-383.

Peng TANG, Weihua LAN, Yao ZHANG, et al. Hereditary pheochromocytoma/paraganglioma and associated syndromes: a clinical and genetic study[J]. Journal of Army Medical University, 2024, 46(4): 377-383.
唐朋, 兰卫华, 张尧, 等. 遗传性嗜铬细胞瘤/副神经节瘤及其相关综合征的临床与遗传学研究[J]. 陆军军医大学学报, 2024,46(4):377-383. DOI： 10.16016/j.2097-0927.202302129.

Peng TANG, Weihua LAN, Yao ZHANG, et al. Hereditary pheochromocytoma/paraganglioma and associated syndromes: a clinical and genetic study[J]. Journal of Army Medical University, 2024, 46(4): 377-383. DOI： 10.16016/j.2097-0927.202302129.

摘要

目的

探讨不同遗传性嗜铬细胞瘤/副神经节瘤(pheochromocytoma/paraganglioma

PCC/PGL)及其相关综合征的临床表型、遗传特征及其治疗随访策略。

方法

共纳入陆军特色医学中心泌尿外科2000年1月至2022年8月临床确诊的44例PCC/PGL患者

收集患者及其家系成员的临床信息

采用二代测序对43例患者进行遗传学检测

以及采用Sanger测序对先证者和家系成员进行突变验证。

结果

共15例患者确诊为遗传性PCC/PGL

其中7例von Hippel-Lindau (VHL)综合征

3例多发性内分泌腺瘤病2型(multiple endocrine neoplasia type 2

MEN2)

5例家族性副神经节瘤综合征。7个VHL综合征家系按照临床表现分别诊断为VHL2A (c.500G>A)、VHL2B (c.239G>T和c.444_457del)和VHL2C (c.293A>G)3种亚型

先证者均接受了手术治疗

2例复发性PCC及多发性肾癌患者还接受了舒尼替尼靶向治疗。3个MEN2家系分别携c.1901G>C、c.1832G>A和c.1901G>A错义突变

临床诊断均符合MEN2A

所有患者接受肾上腺及甲状腺切除手术

其中1例为预防性甲状腺切除。5个家族性副神经节瘤综合征家系中

共检测到4例SDHB突变患者

1例SDHD突变患者(SDHB: c.343C>T

c.541-2A>G

c.575G>A

c.268C>T; SDHD: c.337_340del)

以散发性腹膜后PGL多见。

结论

超过1/3的PCC/PGL患者可携带胚系基因突变

并具有明显的基因型-表型相关性

基因诊断技术在临床精准治疗及随访、遗传咨询等方面具有重要的指导作用。

Abstract

Objective

To summarize and analyze the clinical phenotypes

hereditary features and treatment and follow-up strategies of different hereditary pheochromocytoma/paragangliomas (PCC/PGL) and related syndromes.

Methods

Forty-four clinically diagnosed PCC/PGL patients admitted in our hospital from January 2000 to August 2022 were enrolled

and the clinical data of them and their family members were collected.Second-generation sequencing was performed on 43 patients for genetic detection

and Sanger sequencing was applied to verify the mutation of the probands and family members.

Results

There were 15 patients diagnosed with hereditary PCC/PGL

including 7 cases of von Hippel-Lindau (VHL) syndrome

3 cases of multiple endocrine neoplasia type 2(MEN2)

and 5 cases of familial paraganglioma syndrome.Seven VHL syndrome families were diagnosed as VHL2A (c.500G>A)

VHL2B (c.239G>T and c.444_457del)

and VHL2C (c.293A>G) according to their clinical manifestations.All probands received surgical treatment

and 2 cases of recurrent PCC and the patients with multiple renal cancer also received targeted therapy with sunitinib.Three MEN2 families carried c.1901G>C

c.1832G>A

and c.1901G>A missense mutations

respectively

and were diagnosed with MEN2A clinically.All of them underwent adrenalectomy and thyroidectomy

including one for preventive thyroidectomy.Among the 5 familial paraganglioma syndrome families

4 patients carried SDHB mutations (SDHB: c.343C>T

c.541-2A>G

c.575G>A

c.268C>T) and 1 patient carried an SDHD mutation (SDHD: c.337_340del).Sporadic retroperitoneal PGL were most common.

Conclusion

More than 1/3 of PCC/PGL patients carry germline gene mutations

showing obvious genotype-phenotype correlation.Genetic diagnosis technology plays an important guidance role for clinical precision treatment and follow-up

and genetic counseling.

关键词

Keywords

references

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