Clinical and Molecular Analysis in Patients with Peutz-Jeghers Syndrome

Area of Science:

• Genetics
• Oncology
• Gastroenterology

Background:

• Peutz-Jeghers syndrome (PJS) is a rare inherited disorder associated with an increased risk of various cancers.
• Genetic variants in the STK11 gene are the primary cause of PJS.
• Understanding genotype-phenotype correlations is crucial for patient management and risk assessment.

Purpose of the Study:

• To investigate the clinical manifestations and genetic profiles of PJS patients in Turkey.
• To identify STK11 gene mutations using next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA).
• To analyze genotype-phenotype relationships in PJS.

Main Methods:

• Retrospective analysis of clinical data from 20 PJS patients across 14 families (2011-2021).
• Targeted NGS and MLPA of the STK11 gene for mutation detection.
• Correlation of genetic findings with clinical symptoms, polyp types, and malignancy.

Main Results:

• Initial symptoms typically appeared around 18.9 years, with abdominal pain and intussusception being common.
• Mucocutaneous lesions (85%) and hamartomatous polyps (90%) were prevalent; 4 patients had dysplastic polyps and 3 developed malignancy.
• NGS identified 11 pathogenic and 3 likely pathogenic STK11 mutations, including 3 novel variants. The diagnostic yield was 78.5% for NGS and 85.7% for NGS+MLPA.
• Truncated STK11 mutations were associated with earlier symptom onset and increased cancer risk.

Conclusions:

• This study represents the first PJS case series in Turkey utilizing NGS and MLPA, identifying novel STK11 mutations.
• Confirmed a strong genotype-phenotype correlation, where truncated mutations are linked to more aggressive disease phenotypes.
• Further research into STK11 variants will enhance understanding and management of PJS patients.