Regenerative Medicine Unit, Epithelial Biomedicine Division, Basic Research Department, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Av. Complutense 22, 28040 Madrid, Spain.
Br J Dermatol. 2011 Sep;165(3):683-92. doi: 10.1111/j.1365-2133.2011.10428.x.
Basal epidermolysis bullosa simplex (EBS) is a group of blistering genodermatoses mostly caused by mutations in the keratin genes, KRT5 and KRT14. Recessive mutations represent about 5% of all EBS mutations, being common and specific in populations with high consanguinity, where affected patients show severe phenotypes.
To accomplish the first mutational analysis in patients of Spanish origin with EBS and to delineate a comprehensive genotype-phenotype correlation.
Twenty-one EBS families were analysed. Immunofluorescence mapping at the dermoepidermal junction level was performed on skin biopsies from patients. Mutation screening of the entire coding sequences of KRT5 and KRT14 in genomic DNA was assessed by polymerase chain reaction and direct sequencing.
KRT5 or KRT14 causative mutations were identified in 18 of the 21 EBS families. A total of 14 different mutations were disclosed, of which 12 were dominant missense mutations and two truncating recessive mutations. Five of the 14 mutations were novel including three dominant in KRT5 (p.V186E, p.T321P and p.A428T) and two recessive in KRT14 (p.K116X and p.K250RfsX8). The two patients with EBS carrying homozygous recessive mutations were affected by severe phenotypes and belonged to consanguineous families. All five families with the EBS Dowling-Meara subtype carried recurrent mutations affecting the highly conserved ends of the α-helical rod domain of K5 and K14. The seven mutations associated with the localized EBS subtype were widely distributed along the KRT5 and KRT14 genes. Two families with mottled pigmentation carried the P25L mutation in KRT5, commonly associated with this subtype.
This study further confirms the genotype-phenotype correlation established for EBS in other ethnic groups, and is the first in a Mediterranean country (excluding Israel). This study adds two novel recessive mutations to the worldwide record to date, which includes a total of 14 mutations. As in previous reports, the recessive mutations resulted in a lack of keratin K14, giving rise to a generalized and severe presentation.
基底细胞表皮松解症（EBS）是一组水疱性遗传性皮肤病，主要由角蛋白基因 KRT5 和 KRT14 的突变引起。隐性突变约占所有 EBS 突变的 5%，在高近亲结婚的人群中较为常见和特异，受影响的患者表现出严重的表型。
完成西班牙裔 EBS 患者的首次突变分析，并描绘全面的基因型-表型相关性。
分析了 21 个 EBS 家系。对患者皮肤活检进行皮肤表皮连接水平的免疫荧光定位。通过聚合酶链反应和直接测序评估 KRT5 和 KRT14 整个编码序列的基因组 DNA 突变筛查。
在 21 个 EBS 家系中，确定了 KRT5 或 KRT14 的致病突变。共发现 14 种不同的突变，其中 12 种为显性错义突变，2 种为隐性截断突变。14 种突变中有 5 种是新的，包括 KRT5 中的 3 种显性（p.V186E、p.T321P 和 p.A428T）和 KRT14 中的 2 种隐性（p.K116X 和 p.K250RfsX8）。携带纯合隐性突变的 2 名 EBS 患者表现出严重的表型，且属于近亲结婚的家系。所有 5 个 EBS Dowling-Meara 亚型的家系均携带影响 K5 和 K14 高度保守的α-螺旋杆结构域的反复突变。与局限性 EBS 亚型相关的 7 种突变广泛分布于 KRT5 和 KRT14 基因中。2 个伴有斑驳色素沉着的家系携带 KRT5 中的 P25L 突变，这通常与该亚型相关。
本研究进一步证实了在其他种族中建立的 EBS 基因型-表型相关性，这是在一个地中海国家（不包括以色列）进行的首次研究。本研究在全球记录中增加了 2 个新的隐性突变，共计 14 个突变。与以往的报道一样，隐性突变导致角蛋白 K14 的缺失，导致全身性和严重的表现。
