A novel FBN1 mutation causes autosomal dominant Marfan syndrome.
A novel FBN1 mutation causes autosomal dominant Marfan syndrome.
复制标题
一种新的 FBN1 突变导致常染色体显性马凡综合征
DOI：
10.3892/mmr.2017.7544
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发表时间：
2017-11
影响因子：
3.4
通讯作者：
Gong B
中科院分区：
文献类型：
--
作者：
Xiao Y;Liu X;Guo X;Liu L;Jiang L;Wang Q;Gong B
马凡综合征(MFS)是一种遗传性和全身性疾病。据报道，在常染色体显性遗传的MFS病例中，纤维蛋白-1基因(FBN1)的突变约占90%。本研究旨在筛查一个常染色体显性遗传性MFS家系中的FBN1基因突变；研究对象包括2名MFS患者在内的4名个体。家属接受了全面的身体、心血管和眼科检查。基因组DNA样本来自该家族以及383名无关的健康受试者。聚合酶链式反应扩增FBN1编码区，直接测序分析。SIFT和PolyPhen-2被用来预测蛋白质可能的结构和功能变化。在第14外显子发现了一个新的杂合突变c.1708T>；G(p.C570G)，该突变导致密码子570(p.C570G)的半胱氨酸被甘氨酸取代。该突变被证实与该家族中受影响成员的MFS表型有关。然而，未受影响的家庭成员和383名正常对照缺乏这种突变。人类FBN1蛋白的多个序列比对表明，这种新的突变发生在不同物种的FBN1蛋白的一个高度保守的区域内，并可能导致该功能区域的结构变化。本研究丰富了FBN1基因MFS相关突变的谱，有助于提高对MFS分子发病机制和临床诊断的认识。
Marfan syndrome (MFS) is an inherited and systemic disorder. It has been reported that mutations in the fibrillin-1 gene (FBN1) account for ~90% of autosomal dominant cases of MFS. This study was conducted to screen mutations of FBN1 in a Chinese family with autosomal dominant MFS; four individuals including two patients with MFS were recruited. The family members underwent complete physical, cardiovascular and ophthalmologic examinations. Genomic DNA samples were collected from the family along with 383 unrelated healthy subjects. FBN1 coding regions were amplified by polymerase chain reaction and analyzed by direct sequencing. SIFT and PolyPhen-2 were used to predict the possible structural and functional alterations of the protein. A novel heterozygous mutation c.1708 T>G (p.C570G) in exon 14 was identified, which led to a substitution of cysteine by glycine at codon 570 (p.C570G). The mutation was identified as being associated with the MFS phenotype in the affected members of this family. However, the unaffected family members and the 383 normal controls lacked the mutation. Multiple sequence alignment of the human FBN1 protein revealed that this novel mutation occurred within a highly conserved region of the FBN1 protein across different species and may induce structural alterations in this functional domain. The spectrum of MFS-associated mutations in the FBN1 gene has been enriched from this study; this may improve understanding of the molecular pathogenesis and clinical diagnosis of MFS.
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影响因子：
3.9
作者：
Baetens, Machteld;Van Laer, Lut;Coucke, Paul J.
通讯作者：
Coucke, Paul J.
影响因子：
9.8
作者：
Faivre, L.;Collod-Beroud, G.;Boileau, C.
通讯作者：
Boileau, C.
影响因子：
4.4
作者：
DIETZ, HC;MCINTOSH, I;FRANCOMANO, CA
通讯作者：
FRANCOMANO, CA
影响因子：
3.9
作者：
Dietz, Harry C.;Saraiva, Jorge M.;Francomano, Clair A.
通讯作者：
Francomano, Clair A.
影响因子：
5.2
作者：
Tiecke, F;Katzke, S;Rosenberg, T
通讯作者：
Rosenberg, T