| 刘 丹,田孝祥,刘艳霞,刘美丽,闫承慧.中国汉族两个马凡综合征家系FBN1基因的一个新插入突变和一个复发点突变[J].,2017,17(10):1801-1805 |
| 中国汉族两个马凡综合征家系FBN1基因的一个新插入突变和一个复发点突变 |
| A Novel Insertion Variant and a Recurrent Point Mutation in Two Chinese Han Marfan Syndrome Families |
| 投稿时间：2016-07-08 修订日期：2016-07-31 |
| DOI：10.13241/j.cnki.pmb.2017.10.001 |
| 中文关键词: 马凡综合征 原纤维蛋白-1 家系 变异 先证者 |
| 英文关键词: Marfan syndrome (MFS) Fibrillin-1 (FBN1) Family Variant Proband |
| 基金项目:国家自然科学基金青年科学基金项目(81500282) |
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| 中文摘要: |
| 摘要 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。 |
| 英文摘要: |
| ABSTRACT Objective: To make genetic diagnosis and discuss the clinical characteristics in two Chinese Han Marfan syndrome (MFS) families. Methods: Family investigation and pedigree analysis was carried out in two MFS families. Variants detection for whole exons of FBN1 gene were performed by polymerase chain reaction and DNA direct sequencing. Functional significances for variants were assessed using by Swiss-model, Polyphen-2 and SIFT software. Results: The two families were characterized as an autosomal dominant inheritance. A de novo variant of FBN1 gene, an insertion A at 1691 base of exon 13 was identified in the patients of family 1 (1691 ins A), which resulted in the premature termination of translation at 571 amino acid. In addition, a known point mutation at exon 27 (3463 G>A) was found in the patients of family 2, which resulted in amino acid change from Asp to Asn at 1155. The two variants were absent in healthy family members and 50 healthy controls. Results of functional significance prediction indicated that these two variants might influence the structure or function of fibrillin-1 protein. Conclusion: A novel insertion variant (1691 ins A) and a known point mutation (3463 G>A) are found in two MFS families. The results enlarge the spectrum of FBN1 gene variants and further support the hypothesis that FBN1 gene variants are pathogenic variants for MFS. |
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