Loss of Dp140 dystrophin isoform and intellectual impairment in Duchenne dystrophy
Loss of Dp140 dystrophin isoform and intellectual impairment in Duchenne dystrophy
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DOI：
10.1212/wnl.55.4.559
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发表时间：
2000-08-22
期刊：
影响因子：
9.9
通讯作者：
Bresolin, N
中科院分区：
文献类型：
--
作者：
Felisari, G;Boneschi, FM;Bresolin, N
背景：精神发育迟滞是Duchenne营养不良（DD）的一个临床特征，约有三分之一的患者患有精神发育迟滞。DNA突变、蛋白质表达和智商分数之间没有明确的联系，尽管有报道称肌营养不良蛋白基因的远端缺失与智力障碍有关。提出了脑远端肌营养不良蛋白亚型Dp140的作用。目的：目的探讨Dp140基因远端部分DNA宏缺失与认知功能障碍的关系。研究方法：66例DD患者接受了韦氏智力量表的一般智力评估，测量全面，言语和操作智商。进行PCR分析以检测肌营养不良蛋白基因的缺失，并在12例患者的亚组中分析Dp140调控区。通过非参数Wilcoxon秩和检验和秩和检验进行统计分析。结果：神经心理学和遗传学数据的比较揭示了远端宏缺失与认知障碍之间的关联（p < 0.001）。比较涉及Dp140基因区域的缺失与推测不改变Dp140表达的缺失导致更大的显著性。结论：这些数据表明，在DD，远端肌营养不良蛋白缺失与智力障碍。这项研究强调了大脑远端亚型Dp140在正常认知发育中的可能作用。
Background: Mental retardation is a clinical feature of Duchenne dystrophy (DD) and affects about one-third of patients. No clear association has been found between DNA mutations, protein expression, and IQ scores, although distal deletions in the dystrophin gene have been reported in association with intellectual impairment. A role for the brain distal dystrophin isoform Dp140 was suggested. Objective: To explore the possible association between cognitive impairment and DNA macrodeletions in the distal part of the gene, including Dp140 gene region. Methods: Sixty-six patients with DD received general intelligence assessment by Wechsler Intelligence Scales measuring full, verbal, and performance IQ. PCR analysis was performed to detect deletions in the dystrophin gene, and the Dp140 regulatory region was analyzed in a subgroup of 12 patients. Statistical analysis was performed by nonparametric Wilcoxon rank signed and rank sum tests. Results: Comparison of neuropsychological and genetic data revealed an association between distal macrodeletions and cognitive impairment (p < 0.001). Comparing deletions involving the Dp140 gene region with deletions presumably not altering Dp140 expression resulted in even greater significance. Conclusions: These data suggest that in DD, distal dystrophin deletions are associated with intellectual impairment. This study highlights a possible role for the brain distal isoform Dp140 in normal cognitive development.