Chillón M, Casals T, Giménez J, Nunes V, Estivill X
Molecular Genetics Department, Hospital Duran i Reynals, Barcelona, Spain.
Hum Mutat. 1994;3(3):223-30. doi: 10.1002/humu.1380030308.
In order to determine the spectrum of CF mutations in the Spanish population, we have analysed 40 unrelated Spanish CF patients, with at least one chromosome negative for mutations delta F508, G542X, and N1303K. Exons 1-7,10-14a,15,16,17b,18-21 of the CFTR gene were studied by Single Strand Conformation Polymorphism (SSCP) analysis, using 60 known CF mutations as controls. SSCP screening allowed us to detect 28 different mutations in 52 CF chromosomes, and to identify four new mutations (Q30X in exon 2, A120T in exon 4, 1812-1G-->A in intron 11 and and 3667del4 in exon 19). Further analysis of the four new mutations in a total of 950 Spanish CF chromosomes showed a final frequency of 0.4%, 0.1%, 0.1%, and 0.1% for 1812-1G-->A,Q30X, A120T, and 3667del4, respectively. No mutations were detected in exons 1, 3, 14a, 16, and 18. We have also detected 10 intragenic polymorphisms and DNA sequence variants and have analysed their frequencies in our population. The total of 28 mutations identified in the 80 CF chromosomes highlight the molecular heterogeneity of CF in the Spanish population.
为了确定西班牙人群中囊性纤维化（CF）突变的谱型，我们分析了40例无亲缘关系的西班牙CF患者，这些患者至少有一条染色体不存在ΔF508、G542X和N1303K突变。采用单链构象多态性（SSCP）分析研究了CFTR基因的外显子1 - 7、10 - 14a、15、16、17b、18 - 21，以60种已知的CF突变作为对照。SSCP筛查使我们在52条CF染色体中检测到28种不同的突变，并鉴定出4种新突变（外显子2中的Q30X、外显子4中的A120T、内含子11中的1812 - 1G→A以及外显子19中的3667del4）。对总共950条西班牙CF染色体上的这4种新突变进行进一步分析，结果显示1812 - 1G→A、Q30X、A120T和3667del4的最终频率分别为0.4%、0.1%、0.1%和0.1%。在外显子1、3、14a、16和18中未检测到突变。我们还检测到10种基因内多态性和DNA序列变异，并分析了它们在我们人群中的频率。在80条CF染色体中鉴定出的总共28种突变突出了西班牙人群中CF的分子异质性。
