Sørensen C B, Ladekjaer-Mikkelsen A S, Andresen B S, Brandrup F, Veien N K, Buus S K, Anton-Lamprecht I, Kruse T, Jensen P K, Eiberg H, Bolund L, Gregersen N
Arhus Universitetshospital, Skejby Sygehus, Molekylaer Medicinsk Forskningsenhed.
Ugeskr Laeger. 2000 Mar 27;162(13):1873-6.
Epidermolysis bullosa simplex (EBS) is a group of autosomal dominant inherited skin disorders caused by mutations in the keratin genes K5 or K14. We examined five Danish families with EBS-Weber-Cockayne (WC) or EBS-Koebner (K) and two sporadic cases of EBS-Dowling-Meara (DM) in order to investigate the mutational spectrum and evaluate the genotype-phenotype correlation in Danish patients. Three new K14 mutations, one new and one previously described K5 mutation were identified by DNA sequence analysis. The positions of the EBS-DM mutations were consistent with previous studies, whereas the EBS-WC and EBS-K mutations were found in regions of the keratin genes not typically associated with this type of EBS mutations. In conclusion, we found a strict genotype-phenotype correlation. Furthermore, we found that the position of the mutation in the keratin gene is not the only determinant for severity of the disease; the nature of the amino acid substitution should also be considered when predicting the severity of the EBS disorder.
单纯性大疱性表皮松解症（EBS）是一组常染色体显性遗传性皮肤病，由角蛋白基因K5或K14突变引起。我们研究了五个患有EBS-韦伯-科凯恩（WC）型或EBS-克布纳（K）型的丹麦家庭以及两例散发的EBS-道林-米拉（DM）型病例，以调查突变谱并评估丹麦患者的基因型-表型相关性。通过DNA序列分析鉴定出三个新的K14突变、一个新的和一个先前描述的K5突变。EBS-DM型突变的位置与先前研究一致，而EBS-WC型和EBS-K型突变则出现在角蛋白基因中通常与这类EBS突变无关的区域。总之，我们发现了严格的基因型-表型相关性。此外，我们发现角蛋白基因中突变的位置并非疾病严重程度的唯一决定因素；在预测EBS疾病的严重程度时，还应考虑氨基酸替代的性质。
