Nelson Isabelle, Stojkovic Tanya, Allamand Valérie, Leturcq France, Bécane Henri-Marc, Babuty Dominique, Toutain Annick, Béroud Christophe, Richard Pascale, Romero Norma B, Eymard Bruno, Ben Yaou Rabah, Bonne Gisèle
Sorbonne Universités,UPMCUniv Paris 06, INSERM UMRS974, CNRS FRE3617, Center of Research in Myology, F-75013 Paris, France.
Institut de Myologie, F-75013, Paris, France.
J Neuromuscul Dis. 2015 Sep 2;2(3):229-240. doi: 10.3233/JND-150093.
Laminin α2 deficient congenital muscular dystrophy, caused by mutations in the LAMA2 gene, is characterized by early muscle weakness associated with abnormal white matter signal on cerebral MRI.
To report on 4 patients with LAMA2 gene mutations whose original clinical features complicated the diagnosis strategy.
Clinical, electrophysiological, muscle imaging and histopathological data were retrospectively collected from all patients. DNA samples were analysed by next-generation sequencing or direct gene sequencing. Laminin α2 was analysed by western-blot and immunohistochemistry.
The four patients achieved independent walking. All had proximal muscle weakness with scapular winging and prominent joint contractures without peripheral neuropathy. During follow-up, two patients suffered from refractory epilepsy associated with brain leukoencephalopathy in one, polymicrogyria and lissencephaly without white matter changes in the other. In two patients, the distribution of fatty infiltration resembles that of collagen-VI related myopathies. Dilated cardiomyopathy contstartabstractwith conduction defects, suggestive of Emery-Dreifuss myopathy, emerged in two of them within the 4th decade. Molecular diagnosis remained elusive for many years. Finally, targeted capture-DNA sequencing unveiled the involvement of the LAMA2 gene in two families, and led us to further identify LAMA2 mutations in the remaining family using Sanger sequencing.
This report extends the clinical and radiological features of partial Laminin α2 deficiency since patients showed atypical manifestations including dilated cardiomyopathy with conduction defects in 2, epilepsy in 2, one of whom also had sole cortical brain abnormalities. Importantly, clinical findings and muscle imaging initially pointed to collagen-VI related disorders and Emery-Dreifuss muscular dystrophy.
由LAMA2基因突变引起的层粘连蛋白α2缺乏型先天性肌营养不良，其特征为早期肌肉无力，并伴有脑部MRI上的白质信号异常。
报告4例LAMA2基因突变患者，其原始临床特征使诊断策略复杂化。
回顾性收集所有患者的临床、电生理、肌肉影像学和组织病理学数据。通过二代测序或直接基因测序分析DNA样本。通过蛋白质免疫印迹法和免疫组织化学法分析层粘连蛋白α2。
4例患者均实现独立行走。所有患者均有近端肌无力，伴有肩胛翼状畸形和明显的关节挛缩，无周围神经病变。在随访期间，2例患者患有难治性癫痫，其中1例伴有脑白质脑病，另1例有多小脑回和无脑回畸形且无白质改变。2例患者的脂肪浸润分布类似于Ⅵ型胶原相关肌病。40岁左右时，其中2例患者出现扩张型心肌病并伴有传导缺陷，提示埃默里-德赖富斯肌营养不良。多年来分子诊断一直难以确定。最后，靶向捕获DNA测序揭示了两个家族中LAMA2基因的受累情况，并促使我们使用桑格测序法在其余家族中进一步鉴定LAMA2突变。
本报告扩展了部分层粘连蛋白α2缺乏的临床和放射学特征，因为患者表现出非典型表现，包括2例伴有传导缺陷的扩张型心肌病、2例癫痫，其中1例还伴有单纯皮质脑异常。重要的是，临床发现和肌肉影像学最初指向Ⅵ型胶原相关疾病和埃默里-德赖富斯肌营养不良。
