Department of Medical Genetics, University of Cambridge, Cambridge, CB2 0QQ, UK.
NIHR Cambridge Biomedical Research Centre, Cambridge, CB2 0QQ, UK.
Hum Mol Genet. 2020 Oct 20;29(R2):R128-R137. doi: 10.1093/hmg/ddaa201.
Over the past two decades advances in genomic technologies have transformed knowledge of the genetic basis of phaeochromocytoma and paraganglioma (PPGL). Though traditional teaching suggested that inherited cases accounted for only 10% of all phaeochromocytoma diagnosis, current estimates are at least three times this proportion. Inherited PPGL is a highly genetically heterogeneous disorder but the most frequently results from inactivating variants in genes encoding subunits of succinate dehydrogenase. Expanding knowledge of the genetics of PPGL has been translated into clinical practice by the provision of widespread testing for inherited PPGL. In this review, we explore how the molecular stratification of PPGL is being utilized to enable more personalized strategies for investigation, surveillance and management of affected individuals and their families. Translating recent genetic research advances into clinical service can not only bring benefits through more accurate diagnosis and risk prediction but also challenges when there is a suboptimal evidence base for the clinical consequences or significance of rare genotypes. In such cases, clinical, biochemical, pathological and functional imaging assessments can all contribute to more accurate interpretation and clinical management.
在过去的二十年中，基因组技术的进步改变了人们对嗜铬细胞瘤和副神经节瘤（PPGL）遗传基础的认识。尽管传统的教学认为遗传性病例仅占所有嗜铬细胞瘤诊断的 10%，但目前的估计至少是这一比例的三倍。遗传性 PPGL 是一种高度遗传异质性疾病，但最常见的是由于琥珀酸脱氢酶亚单位编码基因的失活变异引起的。对 PPGL 遗传的广泛研究已经通过广泛的遗传性 PPGL 检测转化为临床实践。在这篇综述中，我们探讨了 PPGL 的分子分层如何被用于为受影响个体及其家属的调查、监测和管理制定更个性化的策略。将最近的遗传研究进展转化为临床服务不仅可以通过更准确的诊断和风险预测带来好处，而且当罕见基因型的临床后果或意义的证据基础不理想时，也会带来挑战。在这种情况下，临床、生化、病理和功能影像学评估都可以有助于更准确的解释和临床管理。
