Mutations in the proenteropeptidase gene are the molecular cause of congenital enteropeptidase deficiency

Am J Hum Genet. 2002 Jan;70(1):20-5. doi: 10.1086/338456. Epub 2001 Nov 21.


Enteropeptidase (enterokinase [E.C.]) is a serine protease of the intestinal brush border in the proximal small intestine. It activates the pancreatic proenzyme trypsinogen, which, in turn, releases active digestive enzymes from their inactive pancreatic precursors. Congenital enteropeptidase deficiency is a rare recessively inherited disorder leading, in affected infants, to severe failure to thrive. The genomic structure of the proenteropeptidase gene (25 exons, total gene size 88 kb) was characterized in order to perform DNA sequencing in three clinically and biochemically proved patients with congenital enteropeptidase deficiency who were from two families. We found compound heterozygosity for nonsense mutations (S712X/R857X) in two affected siblings and found compound heterozygosity for a nonsense mutation (Q261X) and a frameshift mutation (FsQ902) in the third patient. In accordance with the biochemical findings, all four defective alleles identified are predicted null alleles leading to a gene product not containing the active site of the enzyme. These data provide first evidence that proenteropeptidase-gene mutations are the primary cause of congenital enteropeptidase deficiency.

MeSH terms

  • Alleles
  • Base Sequence
  • Binding Sites / genetics
  • Catalytic Domain / genetics
  • Codon, Nonsense / genetics
  • DNA Mutational Analysis
  • Enteropeptidase / chemistry
  • Enteropeptidase / deficiency*
  • Enteropeptidase / genetics
  • Enzyme Precursors / chemistry
  • Enzyme Precursors / deficiency*
  • Enzyme Precursors / genetics
  • Exons / genetics
  • Failure to Thrive / enzymology
  • Failure to Thrive / genetics
  • Female
  • Frameshift Mutation / genetics
  • Heterozygote
  • Humans
  • Introns
  • Male
  • Metabolism, Inborn Errors / enzymology*
  • Metabolism, Inborn Errors / genetics*
  • Mutation / genetics*
  • Pedigree
  • Polymorphism, Genetic / genetics
  • Polymorphism, Single Nucleotide / genetics


  • Codon, Nonsense
  • Enzyme Precursors
  • Enteropeptidase