Influence of mutation type and location on phenotype in 123 patients with Rett syndrome
Influence of mutation type and location on phenotype in 123 patients with Rett syndrome
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DOI：
10.1055/s-2002-32365
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发表时间：
2002-04-01
期刊：
影响因子：
1.4
通讯作者：
Laccone, F
中科院分区：
文献类型：
--
作者：
Huppke, P;Held, M;Laccone, F
雷特综合征（RTT）是一种神经发育障碍，几乎只影响女孩。它是由编码甲基CpG结合蛋白2（MeCP 2）的MECP 2基因突变引起的。在这项研究中，我们相关的突变类型和位置与123个女孩RTT的表型的严重程度。在所有5岁的女孩中评估了坐、走、说话、手功能、头部生长、癫痫发生和综合严重程度评分的能力，然后与分子遗传学检测结果进行统计学相关。我们发现，携带错义突变或缺失的患者位于缺失热点（MECP2基因的碱基对（bp）1030和1207之间的区域），表现出比其他患者更温和的表型。我们将突变的位置与表型相关联，发现所有导致核定位信号（NLS）编码区完全或部分截短的突变与比其他截短突变更严重的表型相关（p = 0.001）。我们没有发现甲基CpG结合结构域（MBD）突变的患者与转录抑制结构域（TRD）突变的患者之间存在显著差异。我们的结论是突变类型和位置与Rett综合征的表型相关。所有损害核定位信号（NLS）的突变都与更严重的表型相关。
Rett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects girls. It is caused by mutations in the MECP2 gene that encodes the methyl-CpG-binding protein 2 (MeCP2). In this study we correlated mutation type and location with the severity of the phenotype in 123 girls with RTT. The ability to sit, walk, speak, hand function, head growth, occurrence of epilepsy and a combined severity score were assessed in all girls at 5 years of age and then statistically correlated with the results of the molecular genetic tests. We found that patients who carry either missense mutations or deletions located within the hotspot for deletions, an area between the base pairs (bp) 1030 and 1207 of the MECP2 gene, present with a milder phenotype than other patients. We correlated the location of the mutations with the phenotype and found that all mutations that lead to either a complete or partial truncation of the region coding for the nuclear localisation signal (NLS) are associated with a more severe phenotype than other truncating mutations (p = 0.001). We did not find a significant difference between the patients with mutations in the methyl-CpG-binding domain (MBD) and those with mutations in the transcriptional repression domain (TRD). We conclude that mutation type and location correlate with the phenotype in Rett syndrome. All mutations that impair the nuclear localisation signal (NLS) are associated with more severe phenotypes.