Frequency of SMARCB1 mutations in familial and sporadic schwannomatosis
Frequency of SMARCB1 mutations in familial and sporadic schwannomatosis
复制标题
DOI：
10.1007/s10048-012-0319-8
复制
发表时间：
2012-05-01
期刊：
影响因子：
2.2
通讯作者：
Evans, D. Gareth R.
中科院分区：
文献类型：
--
作者：
Smith, Miriam J.;Wallace, Andrew J.;Evans, D. Gareth R.
SMARCB1 基因突变与多种人类肿瘤诱发综合征有关。最近，它们被确定为肿瘤抑制综合征神经鞘瘤病的根本原因。家族性疾病的突变检出率比散发性疾病高得多。我们对一组符合神经鞘瘤病临床诊断标准的家族性和散发性患者进行了广泛的基因检测。在我们目前的队列中，我们发现了 SMARCB1 基因内的新突变，并检测到了先前在其他神经鞘瘤病队列中发现的几种突变。在迄今为止报告的神经鞘瘤病筛查中，包括我们当前的数据集，已在 45% 的家族先证者和 7% 的散发患者中发现 SMARCB1 突变。外显子 1 突变 c.41C > A 和 3' 非翻译区突变 c.*82C > T 是迄今为止在神经鞘瘤病中报道的最常见的变化，表明该基因的 5' 和 3' 部分均存在突变热点。 SMARCB1 突变在很大一部分神经鞘瘤病患者中被发现，但仍有可能发现更多致病基因。
Mutations of the SMARCB1 gene have been implicated in several human tumour predisposing syndromes. They have recently been identified as an underlying cause of the tumour suppressor syndrome schwannomatosis. There is a much higher rate of mutation detection in familial disease than in sporadic disease. We have carried out extensive genetic testing on a cohort of familial and sporadic patients who fulfilled clinical diagnostic criteria for schwannomatosis. In our current cohort, we identified novel mutations within the SMARCB1 gene and detected several mutations that have been previously identified in other schwannomatosis cohorts. Of the schwannomatosis screens reported to date, including our current dataset, SMARCB1 mutations have been found in 45 % of familial probands and 7 % of sporadic patients. The exon 1 mutation, c.41C > A, and the 3' untranslated region mutation, c.*82C > T, are the most common changes reported in schwannomatosis disease so far, indicating mutation hotspots at both 5' and 3' portions of the gene. SMARCB1 mutations are found in a significant proportion of schwannomatosis patients, but there remains the possibility that further causative genes remain to be found.