Apert and Crouzon syndromes: Clinical findings, genes and extracellular matrix
Apert and Crouzon syndromes: Clinical findings, genes and extracellular matrix
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DOI：
10.1097/01.scs.0000157078.53871.11
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发表时间：
2005-05-01
影响因子：
0.9
通讯作者：
Bodo, M
中科院分区：
文献类型：
--
作者：
Carinci, F;Pezzetti, F;Bodo, M
Apert和Crouzon综合征是众所周知的颅狭窄。在过去的10年里，进行了一些研究，以提供更好地了解这些疾病的病因和发病机制。两者都具有常染色体显性传播模式，并且编码成纤维细胞生长因子受体2（FGFR2）的基因突变是大多数患者的原因。然而，事实上，同一个突变可以产生广泛的表型表达，使异常发育的机制更加复杂。细胞外基质（ECM）由蛋白质、糖胺聚糖和细胞因子组成，它们以自分泌和旁分泌方式分泌，并能够修饰ECM。成纤维细胞生长因子在结合FGFR 2之前与ECM的组分硫酸乙酰肝素复合。有资料表明，成纤维细胞和成骨细胞中细胞因子和ECM大分子的表达存在差异。ECM成分的变化可以解释成骨过程的改变，并解释除了FGFR2突变之外的颅骨发育中的病理变化。
Apert and Crouzon syndromes are well known craniostenosis. In the last 10 years several studies were performed to provide a better understanding of the etiology and pathogenesis of these diseases. Both have an autosomal dominant mode of transmission, and a mutation in the gene encoding for the fibroblast growth factor receptor 2 (FGFR2) is the cause in most patients. However, the fact that the same mutation can produce a wide range of phenotypic expression makes the mechanism of anomalous development more complex. The extracellular matrix (ECM) is composed of proteins, glycosaminoglycans, and cytokines that are secreted in an autocrine and paracrine manner and are able to modify the ECM. Fibroblast growth factors are complexed with heparan sulfate, a component of the ECM, before binding the FGFR2. Data exist about different expressions of cytokines and ECM macromolecule in craniostenosis-derived fibroblasts and osteoblasts. Changes in ECM composition could explain the altered osteogenic process and account for pathologic variations in cranial development in addition to the FGFR2 mutations.