Phenotypic variability at the TGF-β1 locus in Camurati-Engelmann disease
Phenotypic variability at the TGF-β1 locus in Camurati-Engelmann disease
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DOI：
10.1007/s00439-001-0644-8
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发表时间：
2001-12-01
期刊：
影响因子：
5.3
通讯作者：
Cormier-Daire, V
中科院分区：
文献类型：
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作者：
Campos-Xavier, AB;Saraiva, JM;Cormier-Daire, V
Camurati-Engelmann病（CED）[OMIM 131300]是一种常染色体显性硬化性骨发育不良，最近归因于染色体19q13.1q13.3上的转化生长因子（TGF-β 1）基因突变。迄今为止，在21个家族中已经确定了5个始终位于TGF-β 1前肽中的突变。在这里，我们报告了一个澳大利亚和六个欧洲家庭的TGF-β 1突变。在7个家族中鉴定出3种不同的突变：即R218 H（家族1）、R218 C（家族2、6、7）和C225 R（家族3、4、5）。在我们的家系中鉴定的三种突变先前已在日本和以色列起源的家庭中观察到，并且R218 C似乎是全球最普遍的突变（17/28个报告的家庭）。突变的性质和临床表现的严重程度之间没有明显的相关性，但观察到明显的家族内临床变异，支持CED的不完全突变。有趣的是，TGF-β 1基因的多态性与疾病的严重程度无关。我们的结论是，CED是一种临床变异性疾病，并且这种临床变异性不能由TGF-β 1基因座的多态性来解释。
Camurati-Engelmann disease (CED) [OMIM 131300] is an autosomal dominant sclerosing bone dysplasia recently ascribed to mutations of the transforming growth factor (TGF-beta1) gene on chromosome 19q13.1q13.3. Five mutations consistently located in the TGF-beta1 propeptide have been hitherto identified in 21 families. Here, we report on TGF-beta1 mutations in one Australian and six European families. Three distinct mutations were identified among seven families: namely, R218H (family 1), R218C (families 2, 6, 7) and C225R (families 3, 4, 5). The three mutations identified in our pedigrees have been previously observed in families of Japanese and Israeli origin and the R218C appears to be the most prevalent mutation worldwide (17/28 reported families). No obvious correlation between the nature of the mutations and the severity of the clinical manifestations could be established, but a marked intrafamilial clinical variability was observed, supporting incomplete penetrance of CED. Interestingly, the polymorphisms in the TGF-beta1 gene showed no correlation with the severity of the disease. We conclude that CED is a clinically variable condition and that this clinical variability is not accounted for by polymorphisms at the TGF-beta1 locus.