Identification of mutations in exons 1 through 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
Identification of mutations in exons 1 through 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
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囊性纤维化跨膜电导调节器 (CFTR) 基因外显子 1 至 8 的突变鉴定。
DOI：
10.1016/0888-7543(91)90504-8
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发表时间：
1991
期刊：
影响因子：
4.4
通讯作者：
Tsui,LC
中科院分区：
文献类型：
--
作者：
Zielenski,J;Bozon,D;Kerem,B;Markiewicz,D;Durie,P;Rommens,JM;Tsui,LC
通过对包括外显子1-8在内的5 '未翻译先导子的测序区域，在导致囊性纤维化（CF）的基因中发现了五种不同的突变。这些明显的突变中有两个是错义突变，一个在外显子3 (Gly到Glu在85位；G85E)，另一个在外显子5 (Gly到Arg在178位；G178R)，两者都导致编码蛋白-囊性纤维化跨膜传导调节因子（CFTR）中相应氨基酸的显著变化。另外两种影响外显子4和5 3 '端的高度保守的RNA剪接连接（621+ 1G→T, 711+ 1G→T），导致可能的剪接缺陷。最后一个突变是外显子4的单碱基对缺失，导致移码。这五个突变占我们加拿大CF家族收集的31条非-ΔF508 CF染色体中的9条，它们在任何正常染色体中都没有发现。其中621+ 1G→T、711+ 1G→T和G85E三种突变存在于法裔加拿大人群中，其中621+ 1G→T最为丰富（57）。CFTR基因还有另外两个序列变异；其中一个（129G→C）位于翻译起始密码子上游4个核苷酸，虽然只存在于CF染色体上，但尚不清楚它是否是致病突变；另一个（R75Q）很可能是编码区内的序列变异。
Five different mutations have been identified in the gene causing cystic fibrosis (CF) through sequencing regions encompassing exons 1–8, including the 5′ untranslated leader. Two of these apparent mutations are missense mutations, one in exon 3 (Gly to Glu at position 85; G85E) and another in exon 5 (Gly to Arg at 178; G178R), both causing significant changes in the corresponding amino acids in the encoded protein—cystic fibrosis transmembrane conductance regulator (CFTR). Two others affect the highly conserved RNA splice junction flanking the 3′ end of exons 4 and 5 (621+ 1G→ T, 711+ 1G→ T), resulting in a probable splicing defect. The last mutation is a single-basepair deletion in exon 4, causing a frameshift. These five mutations account for the 9 of 31 non-ΔF508 CF chromosomes in our Canadian CF family collection and they are not found in any of the normal chromosomes. Three of the mutations, 621+ 1G→ T, 711+ 1G→ T, and G85E, are found in the French-Canadian population, with 621+ 1G→ T being the most abundant (5 7). There are two other sequence variations in the CFTR gene; one of them (129G→ C) is located 4 nucleotides upstream of the proposed translation initiation codon and, although present only on CF chromosomes, it is not clear whether it is a disease-causing mutation; the other (R75Q) is most likely a sequence variation within the coding region.