Molecular and Cytogenetics Unit, Department of Haematology and Genetics, Prince of Wales Hospital, Randwick, Sydney, New South Wales, Australia.
PLoS One. 2010 Jan 20;5(1):e8803. doi: 10.1371/journal.pone.0008803.
A significant component of the variation in cognitive disability that is observed in Duchenne muscular dystrophy (DMD) is known to be under genetic regulation. In this study we report correlations between standardised measures of intelligence and mutational class, mutation size, mutation location and the involvement of dystrophin isoforms.
Sixty two male subjects were recruited as part of a study of the cognitive spectrum in boys with DMD conducted at the Sydney Children's Hospital (SCH). All 62 children received neuropsychological testing from a single clinical psychologist and had a defined dystrophin gene (DMD) mutation; including DMD gene deletions, duplications and DNA point mutations. Full Scale Intelligence Quotients (FSIQ) in unrelated subjects with the same mutation were found to be highly correlated (r = 0.83, p = 0.0008), in contrast to results in previous publications. In 58 cases (94%) it was possible to definitively assign a mutation as affecting one or more dystrophin isoforms. A strong association between the risk of cognitive disability and the involvement of groups of DMD isoforms was found. In particular, improvements in the correlation of FSIQ with mutation location were identified when a new classification system for mutations affecting the Dp140 isoform was implemented.
These data represent one of the largest studies of FSIQ and mutational data in DMD patients and is among the first to report on a DMD cohort which has had both comprehensive mutational analysis and FSIQ testing through a single referral centre. The correlation between FSIQ results with the location of the dystrophin gene mutation suggests that the risk of cognitive deficit is a result of the cumulative loss of central nervous system (CNS) expressed dystrophin isoforms, and that correct classification of isoform involvement results in improved estimates of risk.
已知杜氏肌营养不良症（DMD）患者认知障碍的变化很大一部分受遗传调控。本研究报告了标准化智力测量与突变类型、突变大小、突变位置以及肌营养不良蛋白异构体的参与之间的相关性。
62 名男性受试者作为悉尼儿童医院（SCH）进行的 DMD 男孩认知谱研究的一部分被招募。所有 62 名儿童均由一名临床心理学家进行神经心理测试，并且具有明确的肌营养不良蛋白基因（DMD）突变，包括 DMD 基因突变缺失、重复和 DNA 点突变。具有相同突变的非相关受试者的全量表智商（FSIQ）高度相关（r = 0.83，p = 0.0008），这与以前的出版物结果相反。在 58 例（94%）中，可以明确确定突变是否影响一种或多种肌营养不良蛋白异构体。发现认知障碍的风险与 DMD 异构体组的参与之间存在很强的关联。特别是，当实施影响 Dp140 异构体的突变的新分类系统时，确定了 FSIQ 与突变位置之间相关性的改善。
这些数据代表了 DMD 患者中 FSIQ 和突变数据的最大研究之一，也是第一个报告具有全面突变分析和 FSIQ 测试的 DMD 队列的研究之一，该队列通过单一转诊中心进行。FSIQ 结果与肌营养不良蛋白基因突变位置之间的相关性表明，认知缺陷的风险是中枢神经系统（CNS）表达的肌营养不良蛋白异构体丧失的结果，并且正确分类异构体的参与可提高风险估计。
