Analysis of a Finnish family confirms RHBDF2 mutations as the underlying factor in tylosis with esophageal cancer
Analysis of a Finnish family confirms RHBDF2 mutations as the underlying factor in tylosis with esophageal cancer
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DOI：
10.1007/s10689-012-9532-8
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发表时间：
2012-09-01
期刊：
影响因子：
2.2
通讯作者：
Aaltonen, Lauri A.
中科院分区：
文献类型：
--
作者：
Saarinen, Silva;Vahteristo, Pia;Aaltonen, Lauri A.
食管癌Tylosis合并食管癌Tylosis合并食管癌（TOC）是一种罕见的家族性癌症综合征，以常染色体显性遗传方式，以食管癌易感性和角化性皮肤病变为特征。最近报道了RHBDF2基因的两个杂合错义突变与三个家族的TOC相关：在英国和美国的家族中发现了p.i ile186thr突变，在德国的TOC家族中发现了p.p pro189leu突变。我们的目的是通过筛选先前未报道的芬兰TOC家族中的RHBDF2，在独立材料中验证这些新结果。我们发现了一个新的错义突变p.Asp188Asn，与芬兰家族的TOC分离，有趣的是，检测到的突变改变了位于两个先前报道的突变位点之间的密码子。因此，我们证实了RHBDF2突变是TOC综合征的潜在原因，我们的结果表明，TOC相关突变可能是RHBDF2基因中这个特定位点的特异性突变。这些结果使TOC家族成员的遗传咨询和诊断突变筛查成为可能。
Tylosis with esophageal cancer (TOC) is a rare familial cancer syndrome inherited in an autosomal-dominant manner and characterized by esophageal cancer susceptibility and hyperkeratotic skin lesions. Two heterozygous missense mutations in the RHBDF2 gene were recently reported to be associated with TOC in three families: a p.Ile186Thr mutation was found in families from the UK and the US and a p.Pro189Leu mutation was detected in a German TOC family. We aimed to validate these novel results in an independent material by screening RHBDF2 in a previously unreported Finnish TOC family. We identified a new missense mutation, p.Asp188Asn, segregating with TOC in the Finnish family, and interestingly the detected mutation alters a codon located between the two previously reported mutation sites. Thus, we confirmed RHBDF2 mutations as the underlying cause of the TOC syndrome and our results suggest that the TOC associated mutations might be specific for this particular site in the RHBDF2 gene. These results enable the genetic counseling and diagnostic mutation screening of the members of TOC families.