Concurrent APC and MLH1mutations identified in a family affected with familial adenomatous polyposis / 中华医学遗传学杂志

ABSTRACT

OBJECTIVE To report on concurrent mutations of APC and MLH1 genes identified in a family affected with familial adenomatous polyposis(FAP). METHODS The proband was diagnosed with FAP based on her clinical manifestation, family history and histopathology examination. She developed endometrial epithelial neoplasia(EIN) two years later. With peripheral blood samples collected from her and members of her family, genomic DNA was extracted, and mutations of the APC and MLH1 genes were analyzed by Sanger sequencing. RESULTS Two novel heterozygous mutations were identified respectively in the APC gene(c.637C>T, p.R213X) and the MLH1 gene(c.1153C>T, p.R385C) in the proband. The former has resulted in a truncated protein, while the latter has led to substitution of Arginine by Cystine. CONCLUSION The concurrent mutations of the APC and MLH1 genes probably underline the FAP and Lynch syndrome(LS) in this pedigree. As the first female identified with such mutations, the proband manifested later onset of symptoms with certain degree of variation. For patient with FAP, a detailed family history should be taken.Potential mutation of the APC gene should be screened.Non-intestinal manifestations should be searched. For those who have developed endometrial lesion such as EIN, mutation of the MMR gene (associated with LS) should also be screened.