THE RELATION BETWEEN GENOTYPE AND PHENOTYPE IN CYSTIC-FIBROSIS - ANALYSIS OF THE MOST COMMON MUTATION (DELTA-F508)
THE RELATION BETWEEN GENOTYPE AND PHENOTYPE IN CYSTIC-FIBROSIS - ANALYSIS OF THE MOST COMMON MUTATION (DELTA-F508)
复制标题
DOI：
10.1056/nejm199011293232203
复制
发表时间：
1990-11-29
影响因子：
158.5
通讯作者：
DURIE, P
中科院分区：
文献类型：
--
作者：
KEREM, E;COREY, M;DURIE, P
背景与方法：囊性纤维化的临床表现和患者的基因型均具有异质性，但两者之间的相关性尚不清楚。因此，我们研究了293例囊性纤维化患者的血液样本，寻找7号染色体上最常见的致病突变（. delta . f508）的存在，并将结果与该疾病的临床表现进行了比较。结果：. delta的患病率。F508等位基因在队列中占71%；52%的患者为纯合子突变，40%为杂合子突变，8%的患者有其他未定义的突变。突变为纯合子的患者在较早年龄被诊断为囊性纤维化，并且胰腺功能不全的频率更高；99%的纯合子患者存在胰腺功能不全，但72%的杂合子患者和36%的其他基因型患者存在胰腺功能不全。所有三个基因型组的胰腺功能不全患者具有相似的临床特征，反映在诊断时的早期年龄、诊断时相似的汗液氯化物值、相似的肺部疾病严重程度和相似的体重百分位数。相比之下，杂合子基因型组和其他基因型组中没有胰腺功能不全的患者年龄较大，病情较轻。他们在诊断时汗液氯化物值较低，营养状况正常，经年龄调整后肺功能较好。结论：囊性纤维化患者的可变临床病程可至少部分归因于囊性纤维化基因位点的特定基因型。
Background and Methods: Both the clinical manifestations of cystic fibrosis and the genotypes of patients are heterogeneous, but the associations between the two are not known. We therefore studied blood samples from 293 patients with cystic fibrosis for the presence of the most common disease-causing mutation (.DELTA.F508) on chromosome 7 and compared the results with the clinical manifestations of the disease. Results: The prevalence of the .DELTA.F508 allele in the cohort was 71 percent; 52 percent of the patients were homozygous for the mutation, 40 percent were heterozygous, and 8 percent had other, undefined mutations. The patients who were homozygous for the mutation had received a diagnosis of cystic fibrosis at an earlier age and had a greater frequency of pancreatic insufficiency; pancreatic insufficiency was present in 99 percent of the homozygous patients, but in 72 percent of the heterozygous patients and only 36 percent of the patients with other genotypes. The patients with pancreatic insufficiency in all three genotype groups had similar clinical characteristics, reflected by an early age at diagnosis, similar sweat chloride values at diagnosis, similar severity of pulmonary disease, and similar percentiles for weight. In contrast, the patients in the heterozygous-genotype and other-genotype groups who did not have pancreatic insufficiency were older and had milder disease. They had lower sweat chloride values at diagnosis, normal nutritional status, and better pulmonary function after adjustment for age. Conclusions: The variable clinical course in patients with cystic fibrosis can be attributed at least in part to specific genotypes at the locus of the cystic fibrosis gene.