Gross rearrangements of the MECP2 gene are found in both classical and atypical Rett syndrome patients
Gross rearrangements of the MECP2 gene are found in both classical and atypical Rett syndrome patients
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DOI：
10.1136/jmg.2005.033464
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发表时间：
2006-05-01
影响因子：
4
通讯作者：
Clarke, AJ
中科院分区：
文献类型：
--
作者：
Archer, HL;Whatley, SD;Clarke, AJ
MECP 2突变可在80%的经典Rett综合征（RTT）中识别，但在非典型RTT中不太常见。我们招募了110例符合Rett综合征诊断标准的患者，并将其转诊至卡迪夫进行分子分析，但在这些患者中无法识别MECP 2突变。使用多重连接依赖性探针扩增或定量荧光PCR进行MECP 2的剂量分析。37.8%（14/37）的经典RTT患者和7.5%（4/53）的非典型RTT患者存在大片段缺失。大多数大的缺失在外显子4的缺失倾向区域中含有断点。在所有18例缺失病例和在哥廷根发现的4例大缺失病例中确定了临床表型。5例大缺失患者有额外的先天性异常，这明显多于其他MECP 2突变的RTT患者（2/193; p < 0.0001）。在经典和非典型RTT的分子诊断策略中应包括定量分析。
MECP2 mutations are identifiable in similar to 80% of classic Rett syndrome (RTT), but less frequently in atypical RTT. We recruited 110 patients who fulfilled the diagnostic criteria for Rett syndrome and were referred to Cardiff for molecular analysis, but in whom an MECP2 mutation was not identifiable. Dosage analysis of MECP2 was carried out using multiplex ligation dependent probe amplification or quantitative fluorescent PCR. Large deletions were identified in 37.8% (14/37) of classic and 7.5% (4/53) of atypical RTT patients. Most large deletions contained a breakpoint in the deletion prone region of exon 4. The clinical phenotype was ascertained in all 18 of the deleted cases and in four further cases with large deletions identified in Goettingen. Five patients with large deletions had additional congenital anomalies, which was significantly more than in RTT patients with other MECP2 mutations (2/193; p < 0.0001). Quantitative analysis should be included in molecular diagnostic strategies in both classic and atypical RTT.