Duchenne muscular dystrophy is a multifactorial disease including a cognitive phenotype. It is caused by mutations in the X-chromosomal DMD gene from which dystrophin is synthesized. Multiple isoforms of dystrophin have been identified. The full length dystrophin isoform Dp427m is expressed predominantly in muscle. Other isoforms include: Dp427c, Dp427p, Dp260, Dp140, Dp116, Dp71 and Dp40. The majority of these isoforms are expressed in brain and several hypotheses exist on their role in subtypes of neurons and astrocytes. However, their function in relation to cognition remains unclear. Unlike progressive muscle wasting, cognitive involvement is not seen in all DMD patients and the severity varies greatly. To achieve a better understanding of brain involvement in DMD, a multidisciplinary approach is required. Here, we review the latest findings on dystrophin isoform expression in the brain; specific DMD-associated learning and behavioural difficulties; and imaging and spectroscopy findings relating to brain structure, networks, perfusion and metabolism. The main challenge lies in determining links between these different findings. If we can determine which factors play a role in the differentiation between severe and minor cognitive problems in DMD in the near future, we can both provide better advise for the patients and also develop targeted therapeutic interventions.

中文翻译：

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结合遗传学、神经心理学和神经影像学，以提高对杜氏肌营养不良症大脑参与的理解——叙述性评论

Duchenne 肌营养不良症是一种多因素疾病，包括认知表型。它是由合成抗肌萎缩蛋白的 X 染色体 DMD 基因突变引起的。已经鉴定了多种肌养蛋白同种型。全长肌养蛋白同种型 Dp427m 主要在肌肉中表达。其他同工型包括：Dp427c、Dp427p、Dp260、Dp140、Dp116、Dp71 和 Dp40。大多数这些同工型在大脑中表达，并且存在一些关于它们在神经元和星形胶质细胞亚型中的作用的假设。然而，它们在认知方面的功能仍不清楚。与进行性肌肉萎缩不同，并非在所有 DMD 患者中都观察到认知受累，并且严重程度差异很大。为了更好地了解大脑参与 DMD，需要采用多学科方法。这里，我们回顾了大脑中肌营养不良蛋白同种型表达的最新发现；与 DMD 相关的特定学习和行为困难；以及与大脑结构、网络、灌注和代谢相关的成像和光谱学发现。主要挑战在于确定这些不同发现之间的联系。如果我们能在不久的将来确定哪些因素在区分 DMD 的严重和轻微认知问题中起作用，我们既可以为患者提供更好的建议，也可以制定有针对性的治疗干预措施。