STK11 Causative Variants and Copy Number Variations Identified in Thai Patients With Peutz-Jeghers Syndrome

Area of Science:

• Genetics
• Oncology
• Gastroenterology

Background:

• Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder.
• It is caused by germline mutations in the STK11 tumor suppressor gene.
• PJS presents with gastrointestinal polyps, mucocutaneous pigmentation, and increased cancer risk.

Purpose of the Study:

• To summarize the clinical and molecular characteristics of five Thai PJS patients.
• To identify STK11 mutations in these patients.
• To broaden the understanding of the STK11 mutational and phenotypic spectrum in PJS.

Main Methods:

• Clinical and molecular data from five unrelated Thai PJS patients were analyzed.
• STK11 gene analysis involved DHPLC screening, direct DNA sequencing, and MLPA.
• Copy number variations (CNVs) were also assessed.

Main Results:

• Four pathogenic STK11 alterations were found in the five patients.
• These included two frameshift variants (one novel: c.199dup) and two CNVs (exon 1 deletion, exons 2-3 deletion).
• Exon 1 and exons 2-3 deletions were the most common deleted exons among reported STK11 deletions.

Conclusions:

• All identified STK11 mutations were null mutations.
• These null mutations correlated with more severe PJS phenotypes and cancers.
• The study expands the known phenotypic and mutational spectrum of STK11 in Peutz-Jeghers syndrome.