The microphthalmia-associated transcription factor gene (MITF) belongs to the MYC supergene family and plays an important role in melanocytes’ homeostasis. Individuals harboring MITF germline pathogenic variants are at increased risk of developing cancer, most notably melanoma and renal cell carcinoma. We describe a cohort of ten individuals who harbor the same MITF c.952G > A (p.Glu 318Lys), or p.E318K, germline pathogenic variant. Six carriers developed at least one malignancy (4 cases of breast cancer; 1 cervical cancer; 1 colon cancer; 1 melanoma; 1 ovarian/fallopian tube cancer). A significant phenotypic heterogeneity was found among these individuals and their relatives. Breast cancer was, overall, the most frequent malignancy observed in this case series, with 13 occurrences of 60 (21.67 %) total cancer cases described among the probands and their relatives. Our retrospective analysis data raise the hypothesis of a possible association of the MITF p.E318K pathogenic variant with an increased risk of breast cancer.

中文翻译：

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扩展 E318K (c.952G > A) MITF 种系突变携带者的表型：病例系列和文献回顾

小眼相关转录因子基因 (MITF) 属于 MYC 超基因家族，在黑素细胞的稳态中起重要作用。携带 MITF 种系致病变异的个体患癌症的风险增加，最显着的是黑色素瘤和肾细胞癌。我们描述了一个由 10 个个体组成的队列，这些个体具有相同的 MITF c.952G > A（p.Glu 318Lys）或 p.E318K，种系致病性变异。6 名携带者至少发生了一种恶性肿瘤（4 例乳腺癌；1 例宫颈癌；1 例结肠癌；1 例黑色素瘤；1 例卵巢/输卵管癌）。在这些个体及其亲属中发现了显着的表型异质性。总体而言，乳腺癌是该病例系列中观察到的最常见的恶性肿瘤，发生 13 次，共 60 次 (21. 67 %) 先证者及其亲属中描述的癌症病例总数。我们的回顾性分析数据提出了 MITF p.E318K 致病性变异与乳腺癌风险增加之间可能存在关联的假设。