Background: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease caused by germline mutations of human DNA mismatch repair (MMR) genes. A significant proportion of HNPCC cases are attributed to large genomic rearrangements of MMR genes, but this finding has been less frequently reported in Chinese populations.

Methods: Array-based multiplex ligation-dependent probe amplification (array-MLPA) was employed in this study to detect genomic rearrangements of 82 probands of Chinese HNPCC families.

Results: According to the results, 18 probands harbored germline genomic deletions of MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) genes, accounting for approximately 22% (18/82) of the total subjects. Meanwhile, MSH6 gene deletion occurred only in about 2.4% of the probands (2/82). The deletions of MLH1, MSH2 and MSH6 genes were confirmed by classic MLPA analysis, with a concordance rate of 95.5% (21/22).

Conclusion: Array-MLPA is a highly efficient and precise method for clinical screening and diagnosis of HNPCC. By using this method, we found that the HNPCC families carry deletions of MLH1 and MSH2 genes, which are the major germline genomic aberrations in the studied probands. Nevertheless, the deletion of the MSH6 gene is considered a rare occurrence in Chinese HNPCC families, according to our researche. Despite that, it is of clinical significance to screen and diagnose the HNPCC at the early phase by detecting the germline genomic large aberrations in MSH2/MLH1 genes.