Screening for large mutations of the NF2 gene
Screening for large mutations of the NF2 gene
复制标题
DOI：
10.1002/gcc.20138
复制
发表时间：
2005-04-01
影响因子：
3.7
通讯作者：
Mautner, V
中科院分区：
文献类型：
--
作者：
Kluwe, L;Nygren, AOH;Mautner, V
神经纤维瘤病 2 (NF2) 是一种由 NF2 基因突变失活引起的遗传性疾病，其特征是双侧前庭神经鞘瘤、脊柱肿瘤和其他神经系统良性肿瘤。此前，我们通过基于外显子扫描的方法，在 188 名无关 NF2 患者中的 99 名中发现了基因内 NF2 突变。对 22 名新发 NF2 患者的肿瘤分析发现了 12 种额外的 NF2 突变。使用新开发的基因剂量测定多重连接依赖性探针扩增 (MLPA) 进一步检查其余 77 名患者是否存在较大改变。检测到 1 处单个外显子缺失、7 处多个外显子缺失、7 处涉及 NF2 基因 3' 或 5' 末端的缺失、4 处涉及整个 NF2 基因的缺失以及 1 处三个外显子的重复。对于 77 名患者中的 47 名，可以获得足够质量的 mRNA，从而能够进行转录本分析，这证实了 MLPA 检测到的八个改变。此外，在一个家族中，mRNA 分析检测到另一个基因的两个外显子的插入。因此，在 21 例病例中发现了影响 NF2 基因的缺失、重复和插入，占所研究的 188 名不相关 NF2 患者的 11%，占所识别的 132 个突变的 16%，占外显子扫描未检测到基因内小突变的 77 例病例的 27%。多种筛查技术相结合，使本研究中21例遗传性病例的突变检出率达到100%。 (C) 2005 Wiley-Liss, Inc.
Neurofibromatosis 2 (NF2) is a genetic disorder caused by mutational inactivation of the NF2 gene and is characterized by bilateral vestibular schwannomas, spinal tumors, and other benign tumors of the nervous system. Previously, we found intra-genic NF2 mutations in 99 of 188 unrelated NF2 patients by exon-scanning-based methods. Tumor analysis of 22 de novo NF2 patients led to the identification of 12 additional constitutive NF2 mutations. The remaining 77 patients were further examined for large alterations using the newly developed gene dosage assay multiplex ligation-dependent probe amplification (MLPA). One deletion of a single exon, seven deletions of multiple exons, seven deletions involving the 3' or 5' end of the NF2 gene, four deletions involving the whole NF2 gene, and one duplication of three exons were detected. For 47 of the 77 patients, mRNA of adequate quality could be obtained, enabling transcript analysis, which confirmed eight alterations detected by MLPA. In addition, in one family, the mRNA analysis detected an insertion of two exons of another gene. Thus, deletions, duplications, and insertions affecting the NF2 gene were found in 21 cases, which is 11% of the 188 unrelated NF2 patients studied, 16% of the 132 mutations identified, and 27% of the 77 cases in which no intragenic small mutations were detected by exon scanning. The combination of multiple screening techniques facilitated a mutation-detection rate of 100% for the 21 inherited cases in this study. (C) 2005 Wiley-Liss, Inc.