A novel mutation in the STK11 gene causes heritable Peutz-Jeghers syndrome - a case report

BMC Med Genet. 2017 Feb 23;18(1):19. doi: 10.1186/s12881-017-0373-z.

Abstract

Background: Peutz-Jeghers syndrome (PJS) is a rare disorder characterized by multiple gastrointestinal hamartomatous polyps and mucocutaneous pigmentation. STK11 has been identified as a causative gene for this disease.

Case presentation: Herein we report a Chinese Han kindred with PJS. Onset for the PJS signs in three of the patients was rarely as early as at birth. We identified a novel heterozygous mutation (c.440_441delGT, p.Arg147Leufs*15) in the gene STK11, causing a short frameshift followed by a deletion of 63% of the amino acids in the STK protein. This mutation co-segregated with the PJS phenotype, and was absent in two hundred of unrelated ethnicity-matched controls. The mutation led to expression decrease of unaffected STK11 protein in patients than in controls, as well in PJ polyps than in circulating leucocytes from the patients. Phosphorylation levels of the downstream kinase AMPKα altered according with the expression of STK11. These results indicated the possibility that haploinsufficiency and epigenetic reduction of STK11 contributed to the pathogenesis of the disease.

Conclusion: This study identifies a novel mutation in the pathogenic gene STK11 leading to PJS.

Keywords: Case report; Frameshift mutation; Peutz-Jeghers syndrome; STK11; Truncating mutation.

Publication types

  • Case Reports

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Adolescent
  • Base Sequence
  • DNA / chemistry
  • DNA / isolation & purification
  • DNA / metabolism
  • Exons
  • Frameshift Mutation
  • Germ-Line Mutation*
  • Heterozygote
  • Humans
  • Male
  • Pedigree
  • Peutz-Jeghers Syndrome / diagnosis
  • Peutz-Jeghers Syndrome / genetics*
  • Peutz-Jeghers Syndrome / pathology
  • Protein Serine-Threonine Kinases / genetics*
  • Sequence Analysis, DNA

Substances

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