Allamand V, Sunada Y, Salih M A, Straub V, Ozo C O, Al-Turaiki M H, Akbar M, Kolo T, Colognato H, Zhang X, Sorokin L M, Yurchenco P D, Tryggvason K, Campbell K P
Howard Hughes Medical Institute and Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City 52242, USA.
Hum Mol Genet. 1997 May;6(5):747-52. doi: 10.1093/hmg/6.5.747.
Congenital muscular dystrophy (CMD) is a group of clinically and genetically heterogeneous disorders inherited in an autosomal recessive mode. The alpha2-chain of laminin-2 (previously called merosin) has been shown by immunohistochemical and genetic analyses to be implicated in the pathogenesis of the 'classic' form of CMD. In the 'merosin-deficient' subgroup, which represents about half of the cases, more definite evidence of the involvement of the laminin alpha2-chain has recently been reported with the identification of mutations in the gene encoding the alpha2-chain of laminin 2 (LAMA2) in CMD patients. Here we report on two siblings from a consanguineous family expressing an internally deleted laminin alpha2-chain as a result of a splice site mutation in the LAMA2 gene which causes the splicing of exon 25. The predicted protein lacks 63 amino acids in domain IVa which forms a globular structure on the short arm of the alpha2-chain. Interestingly, these patients appear mildly affected compared to others who completely lack this protein. This situation presents a striking analogy with Becker muscular dystrophy, where in-frame deletions in the dystrophin gene result in the expression of a semi-functional protein and lead to a mild phenotype.
先天性肌营养不良（CMD）是一组以常染色体隐性模式遗传的临床和基因异质性疾病。免疫组化和基因分析表明，层粘连蛋白-2的α2链（以前称为merosin）与“经典”型CMD的发病机制有关。在占病例约一半的“merosin缺陷”亚组中，最近有报道称，随着CMD患者中层粘连蛋白α2链（LAMA2）编码基因突变的鉴定，层粘连蛋白α2链受累的证据更加明确。在此，我们报告了来自一个近亲家庭的两名同胞，由于LAMA2基因中的剪接位点突变导致外显子25的剪接，从而表达了一种内部缺失的层粘连蛋白α2链。预测的蛋白质在IVa结构域中缺少63个氨基酸，该结构域在α2链的短臂上形成一个球状结构。有趣的是，与完全缺乏这种蛋白质的其他患者相比，这些患者的症状似乎较轻。这种情况与贝克肌营养不良症有着惊人的相似之处，在贝克肌营养不良症中，肌营养不良蛋白基因的框内缺失导致一种半功能性蛋白质的表达，并导致轻度表型。
