Study on the Application of MLPA Detection for Large Fragment Loss of Mismatch Repair Genes in Chinese HNPCC Families

• Published in: Discovery medicine Vol. 37; no. 194; p. 554
• Main Authors: Huo, Meisi, Zhang, Yi, Liu, Hongdao, Du, Yiqun, Yan, Shiyan
• Format: Journal Article
• Language: English
• Published: United States 01.03.2025
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adult; Asian People - genetics; China; Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics; DNA Mismatch Repair - genetics; DNA-Binding Proteins - genetics; East Asian People; Female; Germ-Line Mutation; Humans; Male; Middle Aged; Multiplex Polymerase Chain Reaction - methods; MutL Protein Homolog 1; MutS Homolog 2 Protein - genetics; Nuclear Proteins - genetics; Pedigree; China; HNPCC; mutation; microarray; MLPA; hereditary nonpolyposis colorectal cancer
• ISSN: 1944-7930
• DOI: 10.24976/Discov.Med.202537194.47

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease caused by germline mutations of human DNA mismatch repair ( ) genes. A significant proportion of HNPCC cases are attributed to large genomic rearrangements of genes, but this finding has been less frequently reported in Chinese populations. 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. According to the results, 18 probands harbored germline genomic deletions of MutL homolog 1 ( ) and MutS homolog 2 ( ) genes, accounting for approximately 22% (18/82) of the total subjects. Meanwhile, gene deletion occurred only in about 2.4% of the probands (2/82). The deletions of , and genes were confirmed by classic MLPA analysis, with a concordance rate of 95.5% (21/22). 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 and genes, which are the major germline genomic aberrations in the studied probands. Nevertheless, the deletion of the 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 genes.