Elastins from patients with Williams–Beuren syndrome and healthy individuals differ on the molecular level
Elastins from patients with Williams–Beuren syndrome and healthy individuals differ on the molecular level
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WilliamsâBeuren 综合征患者和健康个体的弹性蛋白在分子水平上存在差异
DOI：
10.1002/ajmg.a.37638
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发表时间：
2016
影响因子：
2
通讯作者：
C.E.H. Schmelzer
中科院分区：
文献类型：
--
作者：
A. Heinz;A.C. Mora Huertas;C.U. Schräder;R. Pankau;A. Gosch;C.E.H. Schmelzer
Williams-Beuren综合征(WBS)是一种先天性疾病，涉及7号染色体上弹性蛋白基因和其他基因的杂合性缺失。与必要的细胞外基质蛋白弹性蛋白半合子相关的临床症状包括皮肤过早老化和瓣膜上主动脉狭窄。然而，对WBS患者结缔组织结构异常的分子基础知之甚少。因此，这项研究首次旨在系统地描述和比较WBS患者和健康人皮肤和主动脉组织中弹性蛋白的结构和数量。从组织活检中分离出弹性蛋白纤维，发现WBS患者的皮肤与健康人的皮肤相比，弹性蛋白含量显著减少。采用扫描电子显微镜、质谱仪和生物信息学数据分析相结合的方法研究了弹性蛋白的分子结构。扫描电子显微镜显示WBS和健康的弹性蛋白之间有明显的区别。在分子结构方面，发现WBS和健康弹性蛋白的脯氨酸羟化程度不同，而原弹性蛋白亚型似乎是相同的。在交联性方面，WBS和健康弹性蛋白的四官能交联物桥连素和异桥连素的含量没有差异。然而，主成分分析显示，来自健康先证者和WBS患者的弹性蛋白的酶消化不同，这表明对酶切割的敏感性不同。总体而言，这项研究有助于更好地了解WBS患者的基因型别和弹性蛋白相关表型特征之间的相关性。©2016 Wiley期刊，Inc.
Williams–Beuren syndrome (WBS) is a congenital disorder, which involves the heterozygous deletion of the elastin gene and other genes on chromosome 7. Clinical symptoms that are associated with hemizygosity of the essential extracellular matrix protein elastin include premature aging of the skin and supravalvular aortic stenosis. However, only little is known about the molecular basis of structural abnormalities in the connective tissue of WBS patients. Therefore, for the first time this study aimed to systematically characterize and compare the structure and amount of elastin present in skin and aortic tissue from WBS patients and healthy individuals. Elastin fibers were isolated from tissue biopsies, and it was found that skin of WBS patients contains significantly less elastin compared to skin of healthy individuals. Scanning electron microscopy and mass spectrometric measurements combined with bioinformatics data analysis were used to investigate the molecular‐level structure of elastin. Scanning electron microscopy revealed clear differences between WBS and healthy elastin. With respect to the molecular‐level structure, it was found that the proline hydroxylation degree differed between WBS and healthy elastin, while the tropoelastin isoform appeared to be the same. In terms of cross‐linking, no differences in the content of the tetrafunctional cross‐links desmosine and isodesmosine were found between WBS and healthy elastin. However, principal component analysis revealed differences between enzymatic digests of elastin from healthy probands and WBS patients, which indicates differing susceptibility toward enzymatic cleavage. Overall, the study contributes to a better understanding of the correlation between genotypic and elastin‐related phenotypic features of WBS patients. © 2016 Wiley Periodicals, Inc.
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影响因子：
5.4
作者：
Heinz, Andrea;Jung, Michael C.;Schmelzer, Christian E. H.
通讯作者：
Schmelzer, Christian E. H.
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DOI：
10.1016/j.bbagen.2013.01.014
发表时间：
2013
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
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通讯作者：
C.E.H. Schmelzer
影响因子：
2.9
作者：
Getie, M;Schmelzer, CEH;Neubert, RHH
通讯作者：
Neubert, RHH
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DOI：
10.1002/ajmg.1320520307
发表时间：
1994
期刊：
American journal of medical genetics
影响因子：
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作者：
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通讯作者：
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影响因子：
3.4
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