Kremer H, Zeeuwen P, McLean W H, Mariman E C, Lane E B, van de Kerkhof C M, Ropers H H, Steijlen P M
Department of Human Genetics, University Hospital Nijmegen, The Netherlands.
J Invest Dermatol. 1994 Sep;103(3):286-9. doi: 10.1111/1523-1747.ep12394414.
Ichthyosis bullosa of Siemens is a blistering disorder with autosomal dominant inheritance. The disease resembles bullous congenital ichthyosiform erythroderma but is less severe. Keratins K1 and K10 have been implicated in bullous congenital ichthyosiform erythroderma. Linkage analysis pointed to the involvement of a keratin type II gene (12q11-13) in ichthyosis bullosa of Siemens. Mutations in the highly conserved regions of K1, a member of the type II gene cluster, were excluded. The gene coding for keratin 2e is also located in the type II gene cluster and the expression of the gene coincides with the occurrence of epidermolytic hyperkeratosis. Sequence analysis revealed the presence of mutations in the K2e gene in patients with ichthyosis bullosa of Siemens. Three different mutations were detected, one in the 1A domain and two in the 2B domain of the rod. Furthermore, histologic and ultrastructural examination of skin biopsies indicated that ichthyosis exfoliativa is identical to ichthyosis bullosa of Siemens. This was confirmed by the results of the molecular analysis. In the family diagnosed as ichthyosis exfoliativa, a mutation was detected that was identical to the mutation found in one of the families with ichthyosis bullosa of Siemens.
西门斯大疱性鱼鳞病是一种具有常染色体显性遗传的水疱性疾病。该疾病类似于大疱性先天性鱼鳞病样红皮病，但症状较轻。角蛋白K1和K10与大疱性先天性鱼鳞病样红皮病有关。连锁分析表明，一种II型角蛋白基因（12q11 - 13）与西门斯大疱性鱼鳞病有关。II型基因簇成员K1高度保守区域的突变被排除。编码角蛋白2e的基因也位于II型基因簇中，且该基因的表达与表皮松解性角化过度的发生一致。序列分析显示，西门斯大疱性鱼鳞病患者的K2e基因存在突变。检测到三种不同的突变，一种在杆状区的1A结构域，两种在2B结构域。此外，皮肤活检的组织学和超微结构检查表明，剥脱性鱼鳞病与西门斯大疱性鱼鳞病相同。分子分析结果证实了这一点。在被诊断为剥脱性鱼鳞病的家族中，检测到一个与西门斯大疱性鱼鳞病家族之一中发现的突变相同的突变。
