Molecular consequences of cystic fibrosis transmembrane regulator (CFTR) gene mutations in the exocrine pancreas
Molecular consequences of cystic fibrosis transmembrane regulator (CFTR) gene mutations in the exocrine pancreas
复制标题
DOI：
10.1136/gut.52.8.1159
复制
发表时间：
2003-08-01
期刊：
影响因子：
24.5
通讯作者：
Durie, P
中科院分区：
文献类型：
--
作者：
Ahmed, N;Corey, M;Durie, P
背景和目标：我们测试的假设，囊性纤维化跨膜调节基因突变的实际或预测的后果与胰腺表型和定量外分泌胰腺functions.Methods的措施：我们评估了742例囊性纤维化的基因型和临床资料。在诊断时，610胰腺不足，110胰腺足够，和22胰腺足够的患者发展为胰腺insufficient.Results：我们确定了633例（85.3%），在一个等位基因95（12.8%），在两个等位基因14（1.9%）的突变。鉴定了76种不同的突变。最常见的突变是DeltaF 508（71.3%），其次是G551 D（2.9%）、G542 X（2.3%）、621+1G-->T（1.2%）和W1282 X（1.2%）。根据每个突变的预测功能后果，将患者分为五类。超过95%的严重I、II和III类突变患者为胰腺功能不全或进展为胰腺功能不全。相比之下，患有轻度IV和V类突变的患者的胰腺始终足够。在所有的情况下，但四个基因型与胰腺表型专门。在93例患者中可获得腺泡和导管分泌物的定量数据。与属于I类，II类和III类突变的患者大大降低了腺泡和导管的功能与IV类或V突变。结论：预测或已知的功能后果的特定突变等位基因与胰腺疾病的严重程度囊性纤维化。
Background and aims: We tested the hypothesis that the actual or predicted consequences of mutations in the cystic fibrosis transmembrane regulator gene correlate with the pancreatic phenotype and with measures of quantitative exocrine pancreatic function.Methods: We assessed 742 patients with cystic fibrosis for whom genotype and clinical data were available. At diagnosis, 610 were pancreatic insufficient, 110 were pancreatic sufficient, and 22 pancreatic sufficient patients progressed to pancreatic insufficiency after diagnosis.Results: We identified mutations on both alleles in 633 patients (85.3%), on one allele in 95 (12.8%), and on neither allele in 14 (1.9%). Seventy six different mutations were identified. The most common mutation was DeltaF508 (71.3%) followed by G551D (2.9%), G542X (2.3%), 621+1G-->T (1.2%), and W1282X (1.2%). Patients were categorized into five classes according to the predicted functional consequences of each mutation. Over 95% of patients with severe class I, II, and III mutations were pancreatic insufficient or progressed to pancreatic insufficiency. In contrast, patients with mild class IV and V mutations were consistently pancreatic sufficient. In all but four cases each genotype correlated exclusively with the pancreatic phenotype. Quantitative data of acinar and ductular secretion were available in 93 patients. Patients with mutations belonging to classes I, II, and III had greatly reduced acinar and ductular function compared with those with class IV or V mutations.Conclusion: The predicted or known functional consequences of specific mutant alleles correlate with the severity of pancreatic disease in cystic fibrosis.