Freitas-Castro Felipe, Almeida Madson Q
Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brazil.
Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brazil; Unidade de Oncologia Endócrina, Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-000, Brazil.
Best Pract Res Clin Endocrinol Metab. 2025 Jan;39(1):101922. doi: 10.1016/j.beem.2024.101922. Epub 2024 Aug 14.
Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with clinical heterogeneity and a high association with hereditary disease, affecting approximately 30 % of the cases. Differences in the presentation and genetic etiologies of PPGLs have been demonstrated between Chinese and European patients. The frequency of germline genetic diagnosis was remarkably higher in Brazilian patients (∼50 %) compared with other cohorts (Chinese 21 %, European 31 %, and The Cancer Genome Atlas Program cohort 27 %). Interestingly, germline SDHB genetic defects were also more prevalent in Brazilian patients (17 %) with PPGLs when compared with other cohorts (3-9 %). The SDHB exon 1 deletion was responsible for approximately 50 % of the SDHB pathogenic/likely pathogenic variants in Brazilian patients with PPGLs due to a founder effect. The germline SDHB exon 1 deletion represents ∼10 % of the germline drivers in Brazilian patients (and possibly in Latin America). Therefore, a single diagnostic PCR for the SDHB exon 1 deletion might be very useful in clinical practice for genetic testing and counseling of patients with PPGLs in Latin America.
嗜铬细胞瘤和副神经节瘤(PPGLs)是罕见的神经内分泌肿瘤,具有临床异质性且与遗传性疾病高度相关,约30%的病例受其影响。中国和欧洲患者在PPGLs的临床表现和遗传病因方面存在差异。与其他队列(中国21%、欧洲31%和癌症基因组图谱计划队列27%)相比,巴西患者的种系基因诊断频率显著更高(约50%)。有趣的是,与其他队列(3 - 9%)相比,种系SDHB基因缺陷在巴西PPGLs患者中也更普遍(17%)。由于奠基者效应,SDHB外显子1缺失约占巴西PPGLs患者中SDHB致病/可能致病变异的50%。种系SDHB外显子1缺失约占巴西患者(可能在拉丁美洲)种系驱动因素的10%。因此,针对SDHB外显子1缺失的单一诊断性PCR在拉丁美洲PPGLs患者的基因检测和咨询临床实践中可能非常有用。