McGarth J A, Christiano A M, Pulkkinen L, Eady R A, Uitto J
Department of Dermatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
J Invest Dermatol. 1996 May;106(5):1157-9. doi: 10.1111/1523-1747.ep12340210.
Mutations in the genes encoding laminin 5 (LAMA3, LAMB3, and LAMC2) have been delineated in the autosomal recessive blistering skin disorder, junctional epidermolysis bullosa, particularly in the lethal (Herlitz) variant. In this study, we searched for mutations in these genes in two patients with nonlethal forms of junctional epidermolysis bullosa using polymerase chain reaction amplification of genomic DA, followed by heteroduplex analysis and direct automated nucleotide sequencing. Both patients were found to be compound heterozygotes for the same nonsense mutation on one LAMB3 allele, and different missense mutations on the other LAMB3 allele. The combination of a nonsense and a missense mutation in the LAMB3 gene appears to be important in determining the milder clinical phenotype in some cases of the nonlethal forms of junctional epidermolysis bullosa involving abnormalities in laminin 5.
编码层粘连蛋白5（LAMA3、LAMB3和LAMC2）的基因突变已在常染色体隐性遗传性大疱性皮肤病——交界性大疱性表皮松解症中被明确，尤其是在致死性（赫利茨）变种中。在本研究中，我们通过聚合酶链反应扩增基因组DNA，随后进行异源双链分析和直接自动核苷酸测序，在两名非致死性交界性大疱性表皮松解症患者中寻找这些基因的突变。两名患者均被发现为同一LAMB3等位基因上相同无义突变以及另一个LAMB3等位基因上不同错义突变的复合杂合子。在一些涉及层粘连蛋白5异常的非致死性交界性大疱性表皮松解症病例中，LAMB3基因中无义突变和错义突变的组合似乎在决定较轻的临床表型方面很重要。
