Perez A B, Pereira L V, Brunoni D, Zatz M, Passos-Bueno M R
Centro de Geneética Médica (UNIFESP/EPM), São Paulo, Brazil.
Hum Mutat. 1999;13(1):84. doi: 10.1002/(SICI)1098-1004(1999)13:1<84::AID-HUMU15>3.0.CO;2-U.
Marfan Syndrome (MFS) is a connective tissue disease caused by mutations in the fibrillin-1 FBN1) gene. Screening for mutations in all the 65 exons of the FBN1 gene in 34 unrelated patients were performed to compare the efficiency of SSCP versus Heteroduplex analysis and to verify if the spectrum of mutations in Brazilian patients is similar to the one previously reported. Fourteen different band shifts were detected by SSCP analysis; among these only 6 were also were also detected through Heteroduplex analysis, suggesting that SSCP analysis was a more efficient method. Except for one, the molecular alteration was confirmed in the remaining 13 cases by sequencing; five of them were neutral polymorphisms and the eight others are new pathogenic mutations, as follows: 5 missense, one nonsense and two deletions leading to a premature termination codon (PTC). All of them are located in EGF-like-calcium binding motifs (EGF-like-cb). Our findings reinforce that cysteine substitutions and PTC mutations in the region between exons 24-32 are more likely not to be associated with the neonatal phenotypes.
马凡综合征(MFS)是一种由原纤蛋白-1(FBN1)基因突变引起的结缔组织疾病。对34名无亲缘关系的患者的FBN1基因的所有65个外显子进行突变筛查,以比较单链构象多态性(SSCP)与异源双链分析的效率,并验证巴西患者的突变谱是否与先前报道的相似。通过SSCP分析检测到14种不同的条带迁移;其中只有6种也通过异源双链分析检测到,这表明SSCP分析是一种更有效的方法。除1例之外,其余13例的分子改变通过测序得以证实;其中5例为中性多态性,另外8例为新的致病突变,具体如下:5个错义突变、1个无义突变和2个导致提前终止密码子(PTC)的缺失突变。所有这些突变均位于表皮生长因子样钙结合基序(EGF样-cb)中。我们的研究结果进一步证实,外显子24至32之间区域的半胱氨酸替代和PTC突变更有可能与新生儿表型无关。