Genetic testing is recommended for all patients with pheochromocytomas and paragangliomas (PPGL) to establish genotype-phenotype associations. We investigated germline mutations in 59 patients with PPGL at six Korean university hospitals using next-generation sequencing (NGS) targeting 38 PPGL-associated genes, including those recommended by the Korean PPGL Task Force. Germline mutations were identified in 13 patients (22%), and affected four genes: RET, NF1, VHL, and SDHD. Germline mutations were significantly associated with a family history of PPGL, smaller tumor size, and the presence of other types of tumors. Using 95 Korean PPGL cases with germline mutations identified through a literature review and 13 cases from our cohort, we characterized genotype-phenotype correlations. Mutation hotspots were identified in specific codons of RET (codons 631 and 634), VHL (157 and 167), and SDHB (131 and 253). NF1 mutations varied, indicating the absence of common hotspots. These findings highlight the efficacy of the recommended NGS panel for Korean patients with PPGL and the importance of genetic testing in establishing clinical management and personalized therapeutic strategies.

中文翻译：

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韩国嗜铬细胞瘤和副神经节瘤患者的种系突变和表型关联：多中心研究和文献综述。


建议对所有嗜铬细胞瘤和副神经节瘤 (PPGL) 患者进行基因检测，以建立基因型-表型关联。我们使用针对 38 个 PPGL 相关基因（包括韩国 PPGL 工作组推荐的基因）的下一代测序 (NGS)，研究了韩国六所大学医院的 59 名 PPGL 患者的种系突变。在 13 名患者 (22%) 中发现了种系突变，影响了 4 个基因：RET、NF1、VHL 和 SDHD。种系突变与 PPGL 家族史、较小的肿瘤大小以及其他类型肿瘤的存在显着相关。使用通过文献综述确定的 95 例具有种系突变的韩国 PPGL 病例和我们队列中的 13 例，我们描述了基因型-表型相关性。在 RET（密码子 631 和 634）、VHL（157 和 167）和 SDHB（131 和 253）的特定密码子中鉴定出突变热点。 NF1 突变各不相同，表明不存在共同的热点。这些发现强调了推荐的 NGS 组合对韩国 PPGL 患者的疗效以及基因检测在建立临床管理和个性化治疗策略中的重要性。