-
Views
-
Cite
Cite
Junya Yamaguchi, Yuri Sato, Mizuho Kita, Sachio Nomura, Noriko Yamamoto, Yo Kato, Yuichi Ishikawa, Masami Arai, A novel deletion in the splice donor site of MLH1 exon 6 in a Japanese colon cancer patient with Lynch syndrome, Japanese Journal of Clinical Oncology, Volume 45, Issue 10, October 2015, Pages 993–997, https://doi.org/10.1093/jjco/hyv103
Close - Share Icon Share
Abstract
Lynch syndrome is an autosomal dominantly inherited disease that is characterized by a predisposition to cancers, mainly colorectal cancer. Germline mutations of DNA mismatch repair genes such as MLH1, MSH2, MSH6 and PMS2 have been described in patients with Lynch syndrome. Here, we report deletion of 2 bp in the splice donor site of the MLH1 exon 6 (c.545+4_545+5delCA) in a 48-year-old Japanese woman with Lynch syndrome. RT-PCR direct sequencing analysis revealed that this mutation led to an increase in the level of an MLH1 transcript in which exon 6 was skipped, and may cause a frameshift (p.E153FfsX8). Therefore, this mutation appears to be pathogenic and is responsible for Lynch syndrome. Additionally, analysis of the patient's tumor cells indicated microsatellite instability high phenotype and loss of the MLH1 and PMS2 proteins. To our knowledge, this is a germline splice site mutation of MLH1 that has not been reported previously.
- phenotype
- mutation
- cancer
- colorectal cancer
- genetic disorder
- hereditary nonpolyposis colorectal neoplasms
- exons
- frameshift mutation function
- genes
- germ-line mutation
- reverse transcriptase polymerase chain reaction
- tumor cells
- mismatch repair
- microsatellite instability
- pms2 gene
- msh2 gene
- msh6 gene
- splice-site mutation
- donor site
- japanese
