A novel truncating mutation in the E-cadherin gene in the first Iranian family with hereditary diffuse gastric cancer

Aims: Hereditary Diffuse Gastric Cancer (HDGC) is a dominantly inherited familial cancer syndrome resulting from germline mutations of the E-cadherin (CDHI) gene. The first Iranian family with HDGC is herein reported. Methods: The family fulfilled the International Gastric Cancer Linkage Consortium (IGCLC) criteria for HDGC. The entire coding region of the CDHI gene was analysed by direct sequencing in an obligatory carrier. Subsequent molecular genetic tests were done on other at risk individuals to identify mutation carriers. Results: A novel heterozygous 2275G>T mutation in exon 14 of the CDHI gene was detected. This nonsense mutation generates a premature stop codon at position 758 giving rise to a truncated E-cadherin protein lacking cytoplasmic region. The specified mutation was detected in the index case and her asymptomatic son who underwent prophylactic gastrectomy. Conclusion: The first Iranian family with HDGC which carries a novel CDHI germline mutation is reported. (C) 2010 Elsevier Ltd. All rights reserved.