Congenital melanocytic nevi (CMN) are cutaneous malformations whose prevalence is inversely correlated with projected adult size. CMN are caused by somatic mutations, but epidemiological studies suggest that germline genetic factors may influence CMN development. In CMN patients from the U.K., genetic variants in MC1R , such as p.V92M and loss‐of‐function variants, have been previously associated with larger CMN. We analyzed the association of MC1R variants with CMN characteristics in two distinct cohorts of medium‐to‐giant CMN patients from Spain (N  = 113) and from France, Norway, Canada, and the United States (N  = 53), similar at the clinical and phenotypical level except for the number of nevi per patient. We found that the p.V92M or loss‐of‐function MC1R variants either alone or in combination did not correlate with CMN size, in contrast to the U.K. CMN patients. An additional case–control analysis with 259 unaffected Spanish individuals showed a higher frequency of MC1R compound heterozygous or homozygous variant genotypes in Spanish CMN patients compared to the control population (15.9% vs. 9.3%; p  = .075). Altogether, this study suggests that MC1R variants are not associated with CMN size in these non‐UK cohorts. Additional studies are required to define the potential role of MC1R as a risk factor in CMN development.

中文翻译：

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Melanocortin-1受体（MC1R）的基因型与中到大型先天性黑素细胞痣的两个队列的大小无关。

先天性黑素细胞痣（CMN）是皮肤畸形，其患病率与预计的成年人大小成反比。CMN是由体细胞突变引起的，但是流行病学研究表明种系遗传因素可能影响CMN的发育。在英国的CMN患者中，MC1R的遗传变异（例如p.V92M和功能丧失变异）以前曾与较大的CMN相关。我们分析了来自西班牙（N  = 113）和法国，挪威，加拿大和美国（N的两个中至大型CMN患者的两个不同队列中MC1R变异体与CMN特征的关联 = 53），在临床和表型水平上相似，但每位患者的痣数量除外。我们发现，与英国CMN患者相比，单独或联合使用的p.V92M或功能丧失的MC1R变体与CMN大小无关。一项对259名未受影响的西班牙人进行的病例对照分析表明，与对照组相比，西班牙CMN患者中MC1R化合物杂合或纯合变异基因型的频率更高（15.9％对9.3％；p  = .075）。总之，这项研究表明，在这些非英国人群中，MC1R变异体与CMN的大小无关。需要进行其他研究才能确定MC1R的潜在作用 作为CMN发展的风险因素。