Clinical and genetic analysis of Peutz-Jeghers syndrome patients in Taiwan

Abstract

Background/purpose: Peutz-Jeghers syndrome (PJS) is an autosomal dominant inherited disorder that is characterized by intestinal hamartomatous polyps and mucocutaneous pigmentation. Recently, germline mutations in the LKB1 gene have been reported to underlie PJS. The gene that encodes this serine/threonine kinase is located at chromosome 19p13.3. The aim of this study was to investigate the clinical and genetic characteristics of PJS patients in Taiwan.

Methods: We searched the patient database of the National Taiwan University Hospital, a tertiary medical center in Taiwan, between January 1990 and November 2005. Patients' clinical information, demographic data, endoscopic pictures, and outcome were reviewed and analyzed. After obtaining informed consent, DNA and RNA were extracted from peripheral blood mononuclear cells and the LKB1 gene was sequenced.

Results: A total of 14 unrelated patients who fulfilled the diagnostic criteria of PJS were included, and seven of them had genetic analysis performed. Mucocutaneous pigmentation was the most frequent presentation. Hamartomas occur most commonly in the small intestine (86%). Frequent abdominal complications include intussusception and gastrointestinal bleeding. Four germline mutations were found (57.1%). Three resulted in stop codons at codon 60, 162 (novel mutation), and 308. The fourth mutation was a missense mutation at codon 239 (novel mutation).

Conclusion: Compared with other countries, PJS patients in Taiwan tended to have more extensive polyps in the gastrointestinal tract, with intussusception being the most common abdominal symptom. Mutations in the LKB1 gene were identified in 57% of the probands in Taiwan.