Holzinger Andreas, Maier Esther M, Bück Cornelius, Mayerhofer Peter U, Kappler Matthias, Haworth James C, Moroz Stanley P, Hadorn Hans-Beat, Sadler J Evan, Roscher Adelbert A
Department of Pediatrics, Division of Clinical Chemistry and Metabolism, Dr. v. Hauner Children's Hospital, Ludwig-Maximilian-University, Munich, Germany.
Am J Hum Genet. 2002 Jan;70(1):20-5. doi: 10.1086/338456. Epub 2001 Nov 21.
Enteropeptidase (enterokinase [E.C.3.4.21.9]) 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.
肠肽酶（肠激酶[E.C.3.4.21.9]）是近端小肠肠刷状缘的一种丝氨酸蛋白酶。它激活胰腺酶原胰蛋白酶原，进而从其无活性的胰腺前体中释放出活性消化酶。先天性肠肽酶缺乏症是一种罕见的隐性遗传疾病，患病婴儿会出现严重的生长发育迟缓。为了对来自两个家庭的三名临床和生化诊断为先天性肠肽酶缺乏症的患者进行DNA测序，对前肠肽酶基因的基因组结构（25个外显子，基因总大小88 kb）进行了表征。我们在两名患病同胞中发现了无义突变（S712X/R857X）的复合杂合性，并在第三名患者中发现了无义突变（Q261X）和移码突变（FsQ902）的复合杂合性。根据生化研究结果，所鉴定的所有四个缺陷等位基因均预测为无效等位基因，导致基因产物不包含该酶的活性位点。这些数据首次证明前肠肽酶基因突变是先天性肠肽酶缺乏症的主要原因。
