Giliberto Florencia, Ferreiro Verónica, Dalamon Viviana, Szijan Irene
Genetica y Biologia Molecular, Facultad de Farmacia y Bioquímica, Instituto de Neurociencias Aplicadas del Hospital de Clinicas, Universidad de Buenos Aires, Buenos Aires, Argentina.
Neurol Res. 2004 Jan;26(1):83-7. doi: 10.1179/016164104773026589.
Analyses of deletions in the dystrophin gene and of cognitive status were performed on patients with Duchenne (DMD) or Becker (BMD) muscular dystrophy in order to find a correlation between both features. Molecular study by multiplex and simplex PCR of dystrophin exons led to the identification of 51 deletions in 126 unrelated patients. Most of them were frameshift, in full agreement with severe clinical symptoms, three patients with a BMD-like phenotype had in-frame mutations. Deletions were localized with reference to the different dystrophin isoform sequences and were clustered in two main areas, 5' and central+ 3' end of the gene. Cognitive abilities were tested in 47 out of 51 patients with identified mutations, 23 of them being mentally impaired. Comparison of molecular and neuropsychological features showed that deletions localized in central and 3' parts of the gene (18 out of 23) are preferentially associated with mental impairment. Fourteen of them were found in the regulatory and coding sequences for the three CNS specific carboxy terminal isoforms. Therefore, though mutations with variable locations may lead to cognitive impairment, our results show that deletions in the distal portion of the gene are basically related to mental retardation.
为了找出两者之间的关联，我们对杜氏（DMD）或贝克（BMD）型肌营养不良患者进行了肌营养不良蛋白基因缺失分析和认知状态分析。通过对肌营养不良蛋白外显子进行多重和单重PCR的分子研究，在126名无亲缘关系的患者中鉴定出51个缺失。其中大多数是移码突变，这与严重的临床症状完全一致，三名具有BMD样表型的患者存在框内突变。根据不同的肌营养不良蛋白同工型序列对缺失进行定位，并集中在基因的两个主要区域，即5'端和中央+ 3'端。在51名已鉴定出突变的患者中，对47名患者的认知能力进行了测试，其中23名存在智力障碍。分子特征与神经心理学特征的比较表明，位于基因中央和3'部分的缺失（23例中的18例）与智力障碍优先相关。其中14例存在于三种中枢神经系统特异性羧基末端同工型的调控序列和编码序列中。因此，尽管位置不同的突变可能导致认知障碍，但我们的结果表明，基因远端部分的缺失基本上与智力迟钝有关。
