Pheochromocytoma (PCC) is a rare, mostly benign tumour of the adrenal medulla. Hereditary PCC accounts for ~35% of cases and has been associated with germline mutations in several cancer susceptibility genes (e.g., KIF1B, SDHB, VHL, SDHD, RET). We performed whole-exome sequencing in a family with four PCC-affected patients in two consecutive generations and identified a potential novel candidate pathogenic variant in the REXO2 gene that affects splicing (c.531-1G>T (NM 015523.3)), which co-segregated with the phenotype in the family. REXO2 encodes for RNA exonuclease 2 protein and localizes to 11q23, a chromosomal region displaying allelic imbalance in PCC. REXO2 protein has been associated with DNA repair, replication and recombination processes and thus its inactivation may contribute to tumorigenesis. While the study suggests that this novel REXO2 gene variant underlies PCC in this family, additional functional studies are required in order to establish the putative role of the REXO2 gene in PCC predisposition.

中文翻译：

---

REXO2中的种系变异是家族性嗜铬细胞瘤中的新候选基因。

嗜铬细胞瘤（PCC）是一种罕见的肾上腺髓质良性肿瘤。遗传性PCC约占病例的35％，并与几种癌症易感基因（例如KIF1B，SDHB，VHL，SDHD，RET）的种系突变相关。我们在四个连续两个世代受PCC影响的患者的家庭中进行了全外显子测序，并在REXO2基因中鉴定出了可能影响剪接的潜在新候选病原体变体（c.531-1G> T（NM 015523.3）），该变体-与家庭中的表型隔离。REXO2编码RNA核酸外切酶2蛋白，并定位于11q23（一个在PCC中显示等位基因失衡的染色体区域）。REXO2蛋白与DNA修复，复制和重组过程相关，因此其失活可能有助于肿瘤发生。