Published online Oct 21, 2021. doi: 10.3748/wjg.v27.i39.6631
Peer-review started: April 15, 2021
First decision: May 24, 2021
Revised: May 31, 2021
Accepted: August 11, 2021
Article in press: August 11, 2021
Published online: October 21, 2021
Different types of pathogenic mutations may produce different clinical phenotypes, but no exact correlation between Peutz-Jeghers syndrome (PJS) genotype and clinical phenotype has been found so far. So it is necessary to study the correlation between genotype and clinical phenotype of PJS, and explore the internal molecular mechanism of different clinical phenotypes.
The authors included 24 cases of treated PJS cases as study participants, collected peripheral venous blood or normal tissue adjacent to polyps for high-throughput next-generation sequencing (NGS) of 139 hereditary colorectal tumor-related genes including STK11/LKB1 to study the correlation between genotype and clinical phenotype of PJS.
To investigate the correlation between the genotype and clinical phenotype of PJS.
Twenty-four patients with PJS were randomly selected for study inclusion. A total of 139 common hereditary tumor-related genes including STK11/LKB1 were screened and analyzed for pathogenic germline mutations by high-throughput next-generation sequencing (NGS), and the pathogenicity of these mutations was evaluated.
STK11/LKB1 gene mutations were identified in 20 PJS patients, 90% of which were pathogenic mutations. 10 cases had new mutation sites. Pathogenic mutations were significantly less frequent in exon 7 of the STK11/LKB1 gene than in other exons. Truncation mutations were more common in exons 1 and 4, and their pathogenicity was significantly higher than that of missense mutations. We also identified SLX4 gene mutations in PJS patients.
PJS has a relatively complicated genetic background. Changes in the sites responsible for coding functional proteins in exon 1 and exon 4 of STK11/LKB1 may be one of the main causes of PJS. Mutation of the SLX4 gene may help to explain the genetic heterogeneity of PJS.
Exploration of the relationships of clinical phenotypes with different STK11 genotypes, may help to interpret some controversial research results. The detection of SLX4 gene mutations in patients with PJS was reported for the first time.