A novel DCC mutation and genetic heterogeneity in congenital mirror movements
A novel DCC mutation and genetic heterogeneity in congenital mirror movements
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DOI：
10.1212/wnl.0b013e318207b1e0
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发表时间：
2011-01-18
期刊：
影响因子：
9.9
通讯作者：
Roze, E.
中科院分区：
文献类型：
--
作者：
Depienne, C.;Cincotta, M.;Roze, E.
目的：DCC是netrin的受体，netrin是一种引导发育中神经元轴突迁移穿过身体中线的蛋白质。最近在2个先天性镜像运动（MM）家族中发现DCC基因突变。目的是研究3个欧洲家庭MM的临床和遗传特征，并测试这种疾病是否是遗传homogeneous.Methods：我们研究了3个MM家庭，共13个受影响的主题。每例患者都进行了标准化的访谈和神经系统检查，重点是MM的现象和过程。MM的严重程度也进行了评估。在指示病例中进行DCC的分子分析。此外，连锁分析的DCC位点进行了一个大的法国family.Results：MM的临床表现和过程中非常相似，在所有受影响的主题，无论DCC突变状态。然而，在每个家族中观察到MM严重程度的轻微受试者间变异性。多发性骨髓瘤通常发生在婴儿期或儿童早期，不会随时间恶化。MM导致的运动残疾为轻度，仅限于需要双手独立运动的活动。我们在一个意大利MM家族中发现了一个DCC基因的新突变，该突变与同侧皮质脊髓投射异常相关。结论：DCC基因在人类皮质脊髓束的发育中起着重要作用。先天性MM尽管临床上具有同质性，但在遗传上是异质性的。神经病学（R）2011; 76：260-264
Objective: DCC is the receptor for netrin, a protein that guides axon migration of developing neurons across the body's midline. Mutations in the DCC gene were recently identified in 2 families with congenital mirror movements (MM). The objective was to study clinical and genetic characteristics of 3 European families with MM and to test whether this disorder is genetically homogeneous.Methods: We studied 3 MM families with a total of 13 affected subjects. Each patient had a standardized interview and neurologic examination, focusing on the phenomenology and course of the MM. The severity of MM was also assessed. Molecular analysis of DCC was performed in the index cases. In addition, linkage analysis of the DCC locus was performed in a large French family.Results: The clinical expression and course of MM were very similar in all the affected subjects, regardless of DCC mutational status. However, slight intersubject variability in the severity of MM was noted within each family. Onset always occurred in infancy or early childhood, and MM did not deteriorate over time. Motor disability due to MM was mild and restricted to activities that require independent movements of the 2 hands. We found a novel mutation in the DCC gene in an Italian family with MM associated with abnormal ipsilateral corticospinal projection. The DCC locus was excluded in the French family.Conclusion: DCC has a crucial role in the development of corticospinal tracts in humans. Congenital MM is genetically heterogeneous, despite its clinical homogeneity. Neurology (R) 2011; 76:260-264