Morriss Samuel, Beshay Victoria, Leong Huei San, Winship Ingrid
Familial Cancer Centre, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
J Kidney Cancer VHL. 2025 Mar 1;12(1):23-26. doi: 10.15586/jkc.v12i1.381. eCollection 2025.
We report a case of a pathogenic variant c.463+4C>G in the von Hippel-Lindau (VHL) gene identified in a patient presenting with bilateral adrenal tumors, including a histologically confirmed pheochromocytoma with no significant family history of VHL-associated tumors. This same variant was first reported as having pathogenic significance in an unrelated proband with a hemangioblastoma and a family history of pheochromocytoma. In our patient, next-generation sequencing and subsequent RNA (ribonucleic acid) analysis confirmed this mutation to be a pathogenic (class 4) variant in intron 2. The lack of family history of VHL-associated tumors correlated with the proband further suggests that this mutation may have reduced penetrance. This case confirms the pathogenicity of the same previously described variant in the VHL gene and underscores the utility of genetic testing in patients with atypical presentations of adrenal tumors, even in the absence of a relevant family history.
我们报告了1例在1例患有双侧肾上腺肿瘤的患者中鉴定出的冯·希佩尔-林道（VHL）基因致病性变异c.463+4C>G，该患者患有1例经组织学确诊的嗜铬细胞瘤，且无VHL相关肿瘤的显著家族史。同一变异首次报道于1例患有成血管细胞瘤且有嗜铬细胞瘤家族史的无关先证者，具有致病意义。在我们的患者中，二代测序及随后的RNA（核糖核酸）分析证实该突变是内含子2中的致病性（4类）变异。该先证者缺乏VHL相关肿瘤家族史进一步提示该突变可能具有降低的外显率。本病例证实了VHL基因中先前描述的同一变异的致病性，并强调了基因检测在肾上腺肿瘤非典型表现患者中的实用性，即使在没有相关家族史的情况下也是如此。
