Genotype-phenotypic correlation of Peutz-Jeghers syndrome on the example of a series of clinical cases

Abstract

Introduction: Peutz-Jeghers syndrome (PEUTZ-JEGHERS SYNDROME; PJS; OMIM#175200) is hereditary tumor syndrome and is characterized by the occurrence of hamartomatous polyps of gastrointestinal tract, melanocytic pigmentation of the skin and mucous membranes, as well as a high predisposition to malignant tumors of various locations. Despite the fact that the clinical features of PJS are currently well understood, the nature of the variability in the phenotypic manifestations of the disease has not been fully described. Aims: to determine the phenotypic and clinical features in patients with PJS depending on the type of mutation in the STK11 gene. Patients and methods: the clinical and genetic data of 3 patients aged 21, 28 and 39 years with clinical signs of PJS are presented. All patients underwent medical genetic counseling and molecular genetic diagnostics of the STK11 gene using NGS and MLPA methods. Results: large deletions of ex2-8 and ex1 in the STK11 gene were revealed in two patients, and one patient showed a splice site variant c.921-1G > A. The identified variant ex2-8 has not previously been described in international databases. When evaluating the clinical and genetic features, the most severe picture of the disease was in a patient with an extended deletion of exons 2-8, large number of polyps and surgical procedures in history. However, in this case, melanocytic pigmentation became less with age, in contrast to patients with a splice site mutation and a single exon deletion. No cancers were detected in the patients. Conclusion: the molecular genetic test made it possible to confirm the clinical diagnosis of PJS, based on various phenotypic features, and to work out the personalized plan for follow-up. Evaluation of the genotype-phenotype correlations will be possible with the development of a unified register of mutation carriers.