Sewry C A, D'Alessandro M, Wilson L A, Sorokin L M, Naom I, Bruno S, Ferlini A, Dubowitz V, Muntoni F
Department of Paediatrics and Neonatal Medicine, Royal Postgraduate Medical School, London, UK.
Neuropediatrics. 1997 Aug;28(4):217-22. doi: 10.1055/s-2007-973703.
Laminin-2 (merosin) is a heterotrimer composed of alpha 2, beta 1 and gamma 1 chains. Approximately half of the cases with the classical form of congenital muscular dystrophy (CMD) have a deficiency of the laminin alpha 2 chain, encoded by the LAMA2 gene on chromosome 6q22. This disorder is often termed merosin-deficient CMD. Skeletal and cardiac muscle, and the peripheral and central nervous systems, all express laminin alpha 2 and can be affected in merosin-deficient CMD. Normal skin also expresses all three chains of laminin-2 at the epidermal/dermal junction, around hair follicles and in the sensory nerves. Skin biopsies can therefore be used to assess merosin status in patients. We show here an absence of laminin alpha 2 in skin from four cases of CMD with a severe phenotype and abnormal magnetic resonance image (MRI) of the brain, in contrast to normal expression in one case of mild CMD with normal MRI, and in five controls. An additional case of CMD had a partial deficiency of laminin alpha 2 in the skin and severe motor disability, but a normal MRI. Sensory nerves in this case showed normal expression of laminin alpha 2, in contrast to its absence in the severe cases. The expression of laminin beta 1 was also reduced in skin from cases of merosin-deficient CMD. In contrast to human fetal muscle, the laminin alpha 2 protein was not detected in fetal skin up to 23 weeks of gestation. The laminin beta 1 and gamma 1 chains, and the mRNA for laminin alpha 2, however, were present. Studies of mRNA of cultured skin cells suggest that fibroblasts are the major source of laminin alpha 2, not keratinocytes. Our data show that skin is useful for the assessment of merosin status in patients with CMD and that skin fibroblasts may be a useful source of tissue-specific RNA. In addition, we show that there is a tissue-specific difference in the developmental expression of the laminin alpha 2 protein.
层粘连蛋白-2（巢蛋白）是一种由α2、β1和γ1链组成的异源三聚体。约一半典型形式的先天性肌营养不良（CMD）病例存在层粘连蛋白α2链缺陷，该链由位于6号染色体6q22的LAMA2基因编码。这种疾病通常被称为巢蛋白缺乏型CMD。骨骼肌和心肌以及外周和中枢神经系统均表达层粘连蛋白α2，在巢蛋白缺乏型CMD中均可受到影响。正常皮肤在表皮/真皮交界处、毛囊周围和感觉神经中也表达层粘连蛋白-2的所有三条链。因此，皮肤活检可用于评估患者的巢蛋白状态。我们在此展示了4例具有严重表型且脑部磁共振成像（MRI）异常的CMD患者皮肤中层粘连蛋白α2缺失，与之形成对比的是1例MRI正常的轻度CMD患者皮肤中层粘连蛋白α2表达正常，以及5例对照者。另外1例CMD患者皮肤中层粘连蛋白α2部分缺乏且存在严重运动障碍，但MRI正常。该病例的感觉神经中层粘连蛋白α2表达正常，而严重病例中则缺失。巢蛋白缺乏型CMD患者皮肤中层粘连蛋白β1的表达也降低。与人类胎儿肌肉不同，在妊娠23周之前的胎儿皮肤中未检测到层粘连蛋白α2蛋白。然而，层粘连蛋白β1和γ1链以及层粘连蛋白α2的mRNA均存在。对培养的皮肤细胞mRNA的研究表明，成纤维细胞是层粘连蛋白α2的主要来源，而非角质形成细胞。我们的数据表明，皮肤可用于评估CMD患者的巢蛋白状态，并且皮肤成纤维细胞可能是组织特异性RNA的有用来源。此外，我们表明层粘连蛋白α2蛋白的发育表达存在组织特异性差异。
