嗜铬细胞瘤和嗜铬细胞瘤状神经节瘤（PPGLs）是罕见的神经内分泌肿瘤，携带25-40％致病性生殖细胞系基因变异（PGVs）。我们评估了我院追踪治疗的115名已确诊的嗜铬细胞瘤患者（其中14名患者是8个不同家庭的亲属，用于遗传调查）。患有经典的MEN2A/MEN2B表型和有风险的亲属接受了RET原癌基因的直接分析，其余患者的样本提交进行了完整的下一代测序，共包括23个与PPGL相关的基因：ATM、ATR、CDKN2A、EGLN1、FH、HRAS、KIF1B、KMT2D、MAX、MDH2、MERTK、MET、NF1、PIK3CA、RET、SDHA、SDHAF2、SDHB、SDHC、SDHD、TMEM127、TP53和VHL。此外，我们还制定了一种临床判断评分（CJS），以确定患者患有可能的遗传病的概率。结果显示，67名患者（58.3%）至少有一个基因的变异：34名患者（50.7%）只有致病性或可能致病性变异，13名患者（19.4%）有致病性或可能致病性变异和变异意义不明（VUS），20名患者（29.8%）仅携带VUS。PGVs在RET（n = 18;38.3％）、VHL（n = 10;21.3％）、SDHB和NF1（n = 8;17％每个）、MAX、SDHD、TMEM127和TP53（n = 1;2.1％每个）中发现。直接遗传学检测显示91.3％的敏感性，81.2％的特异性和76.4％和93.3％的阳性预测值（PPV）和阴性预测值（NPV）。CJS用于确定不需要遗传学检测的患者具有75％的敏感性，96.4％的特异性，60％和98.2％的PPV和NPV。总之，从巴西115名患者中发现的PPGL生殖细胞系基因变异情况显示出略高的致病性和可能致病性变异的发生率，尤其是在RET基因中。我们建议使用CJS来鉴别不需要进行初步遗传学评估的PPGL患者，以提高检测的特异性并降低成本。©作者（们）。

Pheochromocytoma and paragangliomas (PPGLs) are rare neuroendocrine tumors carrying 25-40% pathogenic germline gene variants (PGVs). We evaluated clinical, laboratory, and germline molecular profile of 115 patients with pathologic (14 patients were relatives from 8 different families recruited for genetic survey) confirmed PPGL followed in our institution. Patients with classic MEN2A/MEN2B phenotypes and at-risk relatives underwent direct analysis of RET proto-oncogene, and the remaining had samples submitted to complete next-generation sequencing aiming 23 PPGL-related genes: ATM, ATR, CDKN2A, EGLN1, FH, HRAS, KIF1B, KMT2D, MAX, MDH2, MERTK, MET, NF1, PIK3CA, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, TP53, and VHL. We also developed a clinical judgment score (CJS) to determine the probability of patients having a potentially hereditary disease. The resulting genetic landscape showed that 67 patients (58.3%) had variants in at least one gene: 34 (50.7%) had exclusively pathogenic or likely pathogenic variants, 13 (19.4%) had pathogenic or likely pathogenic variants and variant of undetermined significance (VUS), and 20 (29.8%) carried only VUS. PGVs were found in RET (n = 18; 38.3%), VHL (n = 10; 21.3%), SDHB and NF1 (n = 8; 17% each), and MAX, SDHD, TMEM127, and TP53 (n = 1; 2.1% each). Direct genetic testing disclosed 91.3% sensitivity, 81.2% specificity, and 76.4% and 93.3% positive predictive value (PPV) and negative predictive values (NPV), respectively. The CJS to identify patients who would not benefit from genetic testing had 75% sensitivity, 96.4% specificity, and 60% and 98.2% PPV and NPV, respectively. In summary, the landscape of PPGL germline gene variants from 115 Brazilian patients resulted in slightly higher prevalent pathogenic and likely pathogenic variants, especially in the RET gene. We suggest a CJS to identify PPGL patients who would not require initial genetic evaluation, improving test specificity and reducing costs.© the author(s).