Elitsur Y, Chertow B C, Jewell R D, Finver S N, Primerano D A
Department of Pediatrics, Marshall University School of Medicine, Huntington, West Virginia 25704-9388, USA.
Pediatr Res. 1998 Dec;44(6):927-30. doi: 10.1203/00006450-199812000-00017.
Hereditary pancreatitis (HP) is the second most common cause of chronic childhood pancreatitis in the United States. Mutations in the cationic trypsinogen gene on chromosome 7 are known to cause HP. We identified four families in West Virginia with symptoms consistent with HP. To determine whether members of these families had defects in the trypsinogen gene, we tested for linkage between the HP gene and simple tandem repeat markers on chromosome 7q and screened for a specific mutation in the cationic trypsinogen gene. Two-point linkage analysis indicated that the disease gene is closely linked to three 7q markers (D7S661, D7S2511, and D7S1805). Restriction fragment length polymorphism analysis showed that all clinically affected members and nonpenetrant carriers from the four families carried a G to A mutation in the third exon of the trypsinogen gene. These findings indicate that this mutation is the cause of HP in the families in our study. The observation that most individuals who carry the mutation have symptoms of HP is consistent with the high but incomplete penetrance of the trait. The presence of a single mutation and a common linked haplotype indicates that the defective allele arose in an ancestor common to all four families.
遗传性胰腺炎（HP）是美国儿童慢性胰腺炎的第二大常见病因。已知7号染色体上的阳离子胰蛋白酶原基因突变会导致HP。我们在西弗吉尼亚州发现了四个有与HP相符症状的家族。为了确定这些家族成员的胰蛋白酶原基因是否存在缺陷，我们检测了HP基因与7号染色体长臂上简单串联重复标记之间的连锁关系，并筛查了阳离子胰蛋白酶原基因中的特定突变。两点连锁分析表明，致病基因与三个7号染色体长臂标记（D7S661、D7S2511和D7S1805）紧密连锁。限制性片段长度多态性分析显示，这四个家族中所有临床患病成员和未发病携带者在胰蛋白酶原基因的第三个外显子中都携带一个从G到A的突变。这些发现表明，这种突变是我们研究中这些家族HP的病因。大多数携带该突变的个体都有HP症状这一观察结果与该性状的高但不完全外显率一致。单一突变和常见连锁单倍型的存在表明，缺陷等位基因出现在所有四个家族的共同祖先中。
