Moizard M P, Billard C, Toutain A, Berret F, Marmin N, Moraine C
Unité de Génétique, Hopital Bretonneau, Tours, France.
Am J Med Genet. 1998 Oct 30;80(1):32-41. doi: 10.1002/(sici)1096-8628(19981102)80:1<32::aid-ajmg6>3.0.co;2-y.
Molecular study and neuropsychological analysis were performed concurrently on 49 patients with Duchenne muscular dystrophy (DMD) in order to find a molecular explanation for the cognitive impairment observed in most DMD patients. Complete analysis of the dystrophin gene was performed to define the localization of deletions and duplications in relation to the different DMD promoters. Qualitative analysis of the Dp71 transcript and testing for the specific first exon of Dp140 were also carried out. Neuropsychological analysis assessed verbal and visuospatial intelligence, verbal memory, and reading skills. Comparison of molecular and psychometric findings demonstrated that deletions and duplications that were localized in the distal part of the gene seemed to be preferentially associated with cognitive impairment. Two altered Dp71 transcripts and two deleted Dp140 DNA sequences were found in four patients with severe cerebral dysfunction. These findings suggest that some sequences located in the distal part of the gene and, in particular, some DMD isoforms expressed in the brain may be related to the cognitive impairment associated with DMD.
对49例杜氏肌营养不良症（DMD）患者同时进行了分子研究和神经心理学分析，以便为大多数DMD患者中观察到的认知障碍找到分子学解释。对肌营养不良蛋白基因进行了全面分析，以确定与不同DMD启动子相关的缺失和重复的定位。还进行了Dp71转录本的定性分析以及Dp140特定第一个外显子的检测。神经心理学分析评估了语言和视觉空间智力、语言记忆和阅读技能。分子学和心理测量结果的比较表明，位于基因远端的缺失和重复似乎与认知障碍优先相关。在4例严重脑功能障碍患者中发现了两个改变的Dp71转录本和两个缺失的Dp140 DNA序列。这些发现表明，位于基因远端的一些序列，特别是在大脑中表达的一些DMD异构体，可能与DMD相关的认知障碍有关。
