一例马凡综合征患儿FBN1基因的突变分析

Mutation analysis of FBN1 gene in a child with Marfan syndrome

目的对1例马凡综合征患儿的原纤维蛋白基因-1（fibrillin-1gene，FBN1）基因进行突变分析，探讨其分子发病机制。方法应用直接测序法RgFBN1基因全部66个外显子进行序列分析。用SIFT与PolyPhen-2软件预测FBN1蛋白的结构和功能变化。结果测序结果显示患儿FBN1基因第32外显子存在c．3998G〉A（p．Cys1333Tyr）杂合错义突变，为未报道过的新突变；而患儿家系正常成员和683名正常对照者均未检出该突变。通过蛋白质同源序列比对分析，发现该突变位点在不同物种的FBN1蛋白中高度保守。SIFT与PolyPhen-2预测该突变位点可能导致FBN1蛋白结构和功能的破坏。结论FBN1基因C．3998G〉A（p．Cys1333Tyr）突变可能为该患儿的致病原因，本研究结果丰富了FBN1基因的突变谱。

Objective To detect potential mutations of fibrillin-1 （FBN1） gene in a child with Marfan syndrome （MFS） and explore its molecular pathogenesis. Methods The 66 exons of the FBN1 gene were analyzed by direct sequencing. SIFT and PolyPhen-2 were used to predict the structural and functional changes at the protein level. Results A novel heterozygous mutation c. 3998 G〉A （p. Cys1333Tyr） was found in exon 32 in the child. The same mutation was not found among his unaffected family members and 683 healthy controls. Multiple sequence alignment showed that this novel mutation was located in a highly conserved region of the FBN1 protein across various species and may induce structural change to a functional domain. Conclusion The novel c. 3998G〉 A （p. Cys1333Tyr） mutation of the FBN1 gene probably predisposed the MFS in the child. Above finding has enriched the spectrum of FBN1 mutations.