A HOMOZYGOUS NONSENSE MUTATION IN THE ALPHA-3 CHAIN GENE OF LAMININ-5 (LAMA3) IN LETHAL (HERLITZ) JUNCTIONAL EPIDERMOLYSIS-BULLOSA
A HOMOZYGOUS NONSENSE MUTATION IN THE ALPHA-3 CHAIN GENE OF LAMININ-5 (LAMA3) IN LETHAL (HERLITZ) JUNCTIONAL EPIDERMOLYSIS-BULLOSA
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DOI：
10.1093/hmg/4.5.959
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发表时间：
1995-05-01
影响因子：
3.5
通讯作者：
CHRISTIANO, AM
中科院分区：
文献类型：
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作者：
KIVIRIKKO, S;MCGRATH, JA;CHRISTIANO, AM
遗传性机械性大疱性疾病，交界性大疱性表皮细胞（JEB），其特征在于皮肤和粘膜的广泛起泡和糜烂。JEB的诊断标志包括皮肤基底膜区的半桥粒中的超微结构异常，以及缺乏针对锚定丝蛋白层粘连蛋白5的抗体染色。因此，编码α 3的三个基因，层粘连蛋白5的β 3和γ 2链，称为LAMA 3、LAMB 3和LAMC 2，是JEB的候选基因。我们以前已经证明了在几个家庭与JEB的LAMB 3和LAMC 2基因突变。我们通过PCR扩增单个LAMAS外显子，然后进行异源双链体分析，从一个受影响的儿童开始突变分析。异源双链体的核苷酸测序鉴定了α 3链结构域I/II内的纯合无义突变。这些发现提供了LAMA 3基因内的无义突变也参与JEB发病机制的第一个证据，并表明层粘连蛋白5的所有三个基因的突变可导致JEB表型。
The inherited mechanobullous disorder, junctional epidermolysis bullosa (JEB), is characterized by extensive blistering and erosions of the skin and mucous membranes, The diagnostic hallmarks of JEB include ultrastructural abnormalities in the hemidesmosomes of the cutaneous basement membrane zone, as well as an absence of staining with antibodies against the anchoring filament protein, laminin 5, Therefore, the three genes encoding alpha 3, beta 3 and gamma 2 chains of laminin 5, known as LAMA3, LAMB3 and LAMC2, are candidate genes for JEB. We have previously demonstrated mutations in the LAMB3 and LAMC2 genes in several families with JEB. We initiated mutation analysis from an affected child by PCR amplification of individual LAMAS exons, followed by heteroduplex analysis, Nucleotide sequencing of heteroduplexes identified a homozygous nonsense mutation within domain I/II of the alpha 3 chain. These findings provide the first evidence that nonsense mutations within the LAMA3 gene are also involved in the pathogenesis of JEB, and indicate that mutations of all three genes of laminin 5 can result in the JEB, phenotype.