Two novel mutations and a new STK11/LKB1 gene isoform in Peutz-Jeghers patients

Hum Mutat. 2002 Jul;20(1):78-9. doi: 10.1002/humu.9046.


Peutz-Jeghers syndrome (PJS) is a rare autosomal dominantly inherited disorder with variable expression and incomplete penetrance characterized by mucocutaneous pigmentation, predisposition to hamartomatous intestinal polyposis, and various other neoplasms. It occurs in approximately 1 in 8,300 to 29,000 live births. In nearly 50% of patients PJS is caused by germ line mutations in the STK11/LKB1 serine/threonine kinase gene, the only kinase gene currently known to act as a tumor suppressor. We have performed a mutation search in the STK11/LKB1 gene in 8 sporadic cases and 3 PJS families using a combination of different screening techniques. We have identified four mutations, two of which I177N and the IVS2+1A->G, were previously unreported. We have also evaluated the presence of cDNA alterations by means of RT-PCR analysis and direct cDNA sequencing and have found two aberrant transcripts in a single PJS case despite the lack of any apparent genomic alteration. Finally, we report the presence of a novel STK11/LKB1 cDNA isoform observed in all the normal subjects studied as well as in the majority of the PJS patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Adolescent
  • Adult
  • Alternative Splicing
  • Animals
  • Blotting, Southern
  • COS Cells
  • Child
  • DNA / chemistry
  • DNA / genetics
  • DNA Mutational Analysis
  • DNA, Complementary / chemistry
  • DNA, Complementary / genetics
  • Humans
  • Middle Aged
  • Mutation
  • Peutz-Jeghers Syndrome / genetics*
  • Peutz-Jeghers Syndrome / pathology
  • Polymorphism, Single-Stranded Conformational
  • Protein Serine-Threonine Kinases / genetics*


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