Saarinen, S., Vahteristo, P., Lehtonen, R. et al. Familial Cancer (2012) 11: 525. doi:10.1007/s10689-012-9532-8
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.