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目的:明确两个中国北方汉族马凡综合征(Marfan syndrome,MFS)家系的临床特点,并对其进行基因诊断。方法:对两个家系进行家系调查和系谱分析,应用聚合酶链式反应-DNA测序方法对原纤维蛋白1基因(Fibrillin-1,FBN1)的所有外显子进行测序。应用Swiss-model、Polyphen-2和SIFT软件对发现的变异位点进行功能预测。结果:两个家系均呈常染色显性遗传特点,在家系1患者中发现一个新的插入突变,即第13外显子1691位碱基处插入碱基A(1691 ins A),导致蛋白在第571位氨基酸处翻译提前终止。此外,在家系2患者中发现一个已知的点突变,即第27外显子第3463位碱基由G变为A(3463 G>A),导致第1155位氨基酸由天冬氨酸变为天冬酰胺。这两个变异位点在家系的健康人及50例健康对照中均未出现。功能预测发现这两个变异位点均可能会影响FBN1蛋白的结构或功能。结论:在两个MFS家系中发现一个新插入突变位点(1691 ins A)和一个已知点突变位点(3463 G>A),为扩大FBN1基因的突变谱及进一步阐明FBN1基因突变在MFS中的作用提供理论依据。
Objective: To identify the clinical features of two Chinese Marfan syndrome (MFS) pedigrees in northern China and to perform gene diagnosis. Methods: Pedigree and pedigree analysis of two pedigrees were performed. All exons of Fibrillin-1 (FBN1) were sequenced by polymerase chain reaction-DNA sequencing. Functional prediction of the identified mutation sites was performed using Swiss-model, Polyphen-2 and SIFT softwares. RESULTS: Both families showed an autosomal dominant inheritance. A novel insertion mutation was found in a pedigree-1 patient, in which base 1691 ins A was inserted at position 1691 of exon 13, Translation at amino acid 571 ended prematurely. In addition, a known point mutation was found in 2 pedigrees, that is, base 3463 of exon 27 changed from G to A (3463 G> A), resulting in the change of amino acid 1155 from aspartate to Asparagine. The two variants were not found in healthy pedigrees and in 50 healthy controls. Functional prediction found that both variants may affect the structure or function of FBN1 protein. Conclusion: A new insertion mutation site (1691 ins A) and a known point mutation site (3463 G> A) were found in two MFS families. In order to expand the mutation spectrum of FBN1 gene and further elucidate the relationship between FBN1 gene mutation and MFS In the role of providing a theoretical basis.