Sossenheimer M J, Aston C E, Preston R A, Gates L K, Ulrich C D, Martin S P, Zhang Y, Gorry M C, Ehrlich G D, Whitcomb D C
Department of Medicine, University of Pittsburgh, Pittsburgh Veterans Affairs Medical Center, Pennsylvania 15261, USA.
Am J Gastroenterol. 1997 Jul;92(7):1113-6.
Because there are no markers for hereditary pancreatitis (HP), diagnosis has relied on clinical features and inferences. Identification of the HP disease gene locus on chromosome 7q35 provides the first genetic marker for HP, allowing an accurate comparison of the clinical diagnosis of HP with the presence of a high-risk HP haplotype. Our objectives were to compare the clinical diagnosis of HP with inheritance of the HP gene and to characterize the common clinical features.
A detailed questionnaire was administered to 102 study participants of a large HP kindred. Blood samples were taken for DNA extraction and high-risk haplotype determination. Clinical findings were compared with the presence of a high-risk haplotype.
A family tree of more than 500 members and eight generations was constructed, and clinical features of the 102 participants were determined. HP occurred before the age of 5 yr in 58% of subjects, who presented with common symptoms of abdominal pain, nausea/vomiting, and frequent attacks. Thirty-five probands, of whom 80% had clinical symptoms, carried the high-risk haplotype, confirming previous estimates of 80% penetrance. Thirty-two of the study participants had been clinically diagnosed with HP, whereas 70 were clinically unaffected. With regard to the presence of the high-risk haplotype, 87.5% of the clinically diagnosed patients were affected by HP (true positive), whereas 12.5% did not carry the high-risk haplotype (false positive). Seven obligate carriers were identified through DNA analysis; three had previously been unrecognized because of lack of affected offspring.
The diagnosis of hereditary pancreatitis on clinical grounds alone may be inaccurate in less severe cases, as is the exclusion of carrier status through family tree analysis. Therefore, a definitive diagnosis of hereditary pancreatitis in equivocal cases or exclusion of a carrier state should include analysis of genetic markers.
由于遗传性胰腺炎（HP）没有标志物，其诊断依赖于临床特征和推断。7号染色体q35区域HP疾病基因位点的鉴定为HP提供了首个遗传标志物，使得能够准确比较HP的临床诊断与高危HP单倍型的存在情况。我们的目的是比较HP的临床诊断与HP基因的遗传情况，并描述常见的临床特征。
对一个大型HP家族的102名研究参与者进行了详细问卷调查。采集血样用于DNA提取和高危单倍型测定。将临床发现与高危单倍型的存在情况进行比较。
构建了一个包含500多名成员和八代人的家族树，并确定了102名参与者的临床特征。58%的受试者在5岁前发生HP，表现为腹痛、恶心/呕吐和频繁发作等常见症状。35名先证者携带高危单倍型，其中80%有临床症状，证实了之前80%外显率的估计。32名研究参与者临床诊断为HP，而70名临床未受影响。关于高危单倍型的存在情况，87.5%临床诊断的患者患有HP（真阳性），而12.5%未携带高危单倍型（假阳性）。通过DNA分析鉴定出7名肯定携带者；其中3名由于缺乏患病后代此前未被识别。
仅基于临床依据诊断遗传性胰腺炎在病情较轻的病例中可能不准确，通过家族树分析排除携带者状态也是如此。因此，在可疑病例中明确诊断遗传性胰腺炎或排除携带者状态应包括遗传标志物分析。
