Genetic determination of exocrine pancreatic function in cystic fibrosis.
Genetic determination of exocrine pancreatic function in cystic fibrosis.
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发表时间：
1992-06
影响因子：
9.8
通讯作者：
P. Kristidis;D. Bozon;M. Corey;D. Markiewicz;J. Rommens;Lap-Chee Tsui;P. Durie
中科院分区：
文献类型：
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作者：
P. Kristidis;D. Bozon;M. Corey;D. Markiewicz;J. Rommens;Lap-Chee Tsui;P. Durie
我们还发现囊性纤维化患者的胰腺功能状态可能与囊性纤维化跨膜电导调节基因突变有关。尽管大多数CF突变--包括最常见的Delta F508--与胰腺功能不全(PI)密切相关，但大约10%的突变等位基因可能导致胰腺功能不全(PS)。为了扩大这一观察范围，对538名有良好记录的胰腺功能状态的CF患者的基因组DNA进行了分析，以寻找他们的CFTR基因的一系列已知突变。在测试的25个突变中，只有20个在这个人群中被发现。它们占CF染色体的84%，其中Delta F508最常见(71%)，其他突变各占不到5%。在394名(73%)患者中，总共可以确定30种不同的、完整的基因型别。数据表明，每种基因只与PI或PS相关，而不是同时与两者关联。因此，这一结果与以下假设相一致，即CF中的PI和PS是由CFTR基因座上的基因决定的；PS表型发生在具有一个或两个轻度CFTR突变的患者中，如R117H、R334W、R347P、A455E和P574H，而PI表型发生在具有两个严重等位基因的患者中，如Delta F508、Delta I507、Q493X、G542X、R553X、W1282X、621+1G--T、1717-1G-A、556delA、3659delC、I148T、G480C、V520F、G551D和R560T。
We showed elsewhere that the pancreatic function status of cystic fibrosis (CF) patients could be correlated to mutations in the CF transmembrane conductance regulator (CFTR) gene. Although the majority of CF mutations--including the most common, delta F508--strongly correlated with pancreatic insufficiency (PI), approximately 10% of the mutant alleles may confer pancreatic sufficiency (PS). To extend this observation, genomic DNA of 538 CF patients with well-documented pancreatic function status were analyzed for a series of known mutations in their CFTR genes. Only 20 of the 25 mutations tested were found in this population. They accounted for 84% of the CF chromosomes, with delta F508 being the most frequent (71%), and the other mutations accounted for less than 5% each. A total of 30 different, complete genotypes could be determined in 394 (73%) of the patients. The data showed that each genotype was associated only with PI or only with PS, but not with both. This result is thus consistent with the hypothesis that PI and PS in CF are predisposed by the genotype at the CFTR locus; the PS phenotype occurs in patients who have one or two mild CFTR mutations, such as R117H, R334W, R347P, A455E, and P574H, whereas the PI phenotype occurs in patients with two severe alleles, such as delta F508, delta I507, Q493X, G542X, R553X, W1282X, 621 + 1G----T, 1717-1G----A, 556delA, 3659delC, I148T, G480C, V520F, G551D, and R560T.