Clinical manifestations and STK11 germline mutations in Taiwanese patients with Peutz-Jeghers syndrome

Abstract

Backgrounds: Clinical manifestations and molecular basis of Taiwanese patients with Peutz-Jeghers syndrome (PJS) were investigated to add the knowledge of phenotype and genotype of the disease.

Methods: Based on the Pathology Data Bank and the Colorectal Cancer Register, we collected their clinical data. The entire coding sequence of the STK11 gene was amplified and analyzed by sequencing using the genomic DNA.

Results: Fifteen patients diagnosed with PJS from 11 unrelated families were collected until 2015. The median age at the onset of symptoms was 19 years with intussusception as the most frequent presenting symptom. Ten patients developing 11 cancers at various anatomical sites, including two cases of sinonasal cancer, two lung cancers, two breast cancers, two rectal cancers, two gynecological cancers and one small bowel cancer. Five of the deceased patients had died of cancers. The median age of diagnosis of first cancer in the probands was 32 years. Seventy patients (7 of 10) diagnosed before age of 40. Mutations found in eight families included five novel mutations (exon 6, c.843 ins G; exon 8, c.2065 delete A; exon 8, c.G923A, nonsense; exon 6, c.748dupA; and mTOR c.5107dupA) and three previously reported mutations. The other three PJS families without detectable STK11 mutations did not develop malignancies so far.

Conclusion: This is the first comprehensive study of patients with Peutz-Jeghers syndrome in the Taiwanese. We have demonstrated that the phenotype of Peutz-Jeghers syndrome varies greatly among the patients. Patients with detectable STK11 mutations have very high risk of developing cancers.

Keywords: Hamartomatous polyps; Peutz–Jeghers syndrome; STK11 gene.