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

Wannasiri Chiraphapphaiboon; Wanna Thongnoppakhun; Thawornchai Limjindaporn; Sunisa Sawasdichai; Ekkapong Roothumnong; Kanjana Prangphan; Benjaporn Pamornpol; Chanin Limwongse; Manop Pithukpakorn

doi:10.7759/cureus.34495

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

Cureus. 2023 Feb 1;15(2):e34495. doi: 10.7759/cureus.34495. eCollection 2023 Feb.

Affiliations

¹ Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, THA.
² Siriraj Genomics, Office of the Dean, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, THA.
³ Division of Medical Genetics, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, THA.

Abstract

Introduction Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disorder caused by germline mutations in the serine-threonine kinase 11 (STK11) tumor suppressor gene. This syndrome is characterized by hamartomatous gastrointestinal polyps, mucocutaneous melanin pigmentation, and a higher risk of developing various cancers. Methods We summarized the clinical and molecular characteristics of five unrelated Thai patients with PJS. Denaturing high-performance liquid chromatography (DHPLC) screening, coupled with direct DNA sequencing and multiplex ligation-dependent probe amplification (MLPA), were applied for the molecular analysis of STK11. Results A total of four STK11 pathogenic changeswere identified in the five PJS patients, including two frameshift variants (a novel c.199dup, p.Leu67ProfsTer96 and a known c.834_835del, p.Cys278TrpfsTer6) and two types of copy number variations (CNV), exon 1 deletion and exons 2-3 deletion. Among reported STK11 exonic deletions, exon 1 and exons 2-3 deletions were found to be the two most commonly deleted exons. Conclusion All identified STK11 mutations were null mutations that were associated with more severe PJS phenotypes and cancers. This study broadens the phenotypic and mutational spectrum of STK11 in PJS.

Keywords: copy number variations; deletions; mutations; peutz-jeghers syndrome; stk11.

Grants and funding

This study was supported by Faculty of Medicine Siriraj Hospital, Mahidol University, Grant Number (IO) R015931033 and Chalermphrakiat Grant, Faculty of Medicine Siriraj Hospital, Mahidol University (to WT, TL, BP, CL and MP)