Clinical and Genetic Study of Children With Peutz-Jeghers Syndrome Identifies a High Frequency of STK11 De Novo Mutation

J Pediatr Gastroenterol Nutr. 2019 Feb;68(2):199-206. doi: 10.1097/MPG.0000000000002166.

Abstract

Objectives: The present study aims to identify the genotype-phenotype correlation in children with Peutz-Jeghers Syndrome (PJS) through the analysis of STK11 gene mutations in the context of clinical and pathological characteristics.

Method: In this observational cohort study, the clinical characteristics of 18 families diagnosed with pediatric PJS were collected. Genomic DNA from the peripheral blood of affected children and their family members was collected. The coding region of STK11 was amplified by PCR and screened for mutation by Sanger sequencing. The families that were negative for STK11 mutation were further assessed by multiplex ligation-dependent probe amplification (MLPA).

Result: Initial presentation in affected children was at 1.6 to 14.2 years and included anemia in 8 patients whereas 6 presented for screening by virtue of family history. All patients underwent endoscopy, colonoscopy, and polypectomy. Polyps were distributed throughout the gastrointestinal (GI) tract, including the small intestine, stomach, colon, and rectum.In the 18 pediatric PJS families, STK11 mutations were detected in 8 families by Sanger sequencing, and large deletions were detected in 3 by MLPA, respectively. Nine of the 11 STK11 mutations were de novo, 3 were novel (c.419T>C:p.L140P, c.314T>G:p.L105X), and (c.488_489insACGG p.L164fs).

Conclusions: Although the main clinical features of pediatric PJS were similar to those of PJS cases in adults, a high frequency of STK11 de novo mutations were encountered in our population of patients with PJS.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Humans
  • Infant
  • Male
  • Multiplex Polymerase Chain Reaction
  • Mutation
  • Pedigree
  • Peutz-Jeghers Syndrome / genetics*
  • Protein Serine-Threonine Kinases / genetics*
  • Sequence Analysis, DNA
  • Sequence Deletion

Substances

  • Protein Serine-Threonine Kinases
  • STK11 protein, human
  • AMP-Activated Protein Kinase Kinases