Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
Clin Genet. 2013 Sep;84(3):244-50. doi: 10.1111/cge.12062. Epub 2012 Dec 27.
The MSH2 c.388_389del mutation has occasionally been described in Lynch families worldwide. At the Portuguese Oncology Institute in Porto, Portugal, we have identified 16 seemingly unrelated families with this germline mutation. To evaluate if this alteration is a founder or a recurrent mutation we performed haplotype analysis in the 16 Portuguese index cases and 55 relatives, as well as in four index cases and 13 relatives reported from Germany, Scotland, England, and Argentina. In the Portuguese families we observed a shared haplotype of approximately 10 Mb and all were originated from the north of Portugal. These results suggest that this alteration is a founder mutation in Portugal with a relatively recent origin. In the reported families outside Portugal with this mutation different haplotype backgrounds were observed, supporting the hypothesis that it occurred de novo on multiple occasions. We also conclude that the high proportion of families with the MSH2 c.388_389del mutation indicates that screening for this alteration as a first step may be cost-effective in the genetic testing of Lynch syndrome suspects of Portuguese ancestry, especially those originating from the north of Portugal.
MSH2 c.388_389del 突变偶尔在全球的 Lynch 家族中被描述。在葡萄牙波尔图的葡萄牙肿瘤研究所，我们已经鉴定出 16 个具有这种种系突变的看似无关的家族。为了评估这种改变是一个创始突变还是一个反复出现的突变，我们对 16 个葡萄牙索引病例和 55 个亲属，以及来自德国、苏格兰、英格兰和阿根廷的 4 个索引病例和 13 个亲属进行了单倍型分析。在葡萄牙家族中，我们观察到了大约 10Mb 的共享单倍型，并且都来自葡萄牙北部。这些结果表明，这种改变是葡萄牙的一个创始突变，起源相对较近。在葡萄牙以外的报道的具有这种突变的家族中，观察到了不同的单倍型背景，支持了它多次发生的假说。我们还得出结论，具有 MSH2 c.388_389del 突变的家族比例很高，这表明在葡萄牙血统的 Lynch 综合征疑似患者的遗传检测中，作为第一步筛查这种改变可能具有成本效益，尤其是那些来自葡萄牙北部的患者。
