ICHTHYOSIS BULLOSA OF SIEMENS - A DISEASE INVOLVING KERATIN 2E
ICHTHYOSIS BULLOSA OF SIEMENS - A DISEASE INVOLVING KERATIN 2E
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DOI：
10.1111/1523-1747.ep12394307
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发表时间：
1994-09-01
影响因子：
6.5
通讯作者：
LEIGH, IM
中科院分区：
文献类型：
--
作者：
MCLEAN, WHI;MORLEY, SM;LEIGH, IM
大疱性鱼鳞病是一种不伴红皮病的先天性大疱性鱼鳞病。与大疱性先天性鱼鳞病样红皮病（BCIE）相比，皮肤受累相对较轻，表皮角化过度（EHK）仅限于表皮的上基底层。在研究的两个家庭中，受影响的患者的基底上细胞中观察到张力丝聚集，表明角蛋白异常。角蛋白2 e是在表皮基底上表达的分化特异性II型角蛋白。K2 e基因的一部分通过聚合酶链反应使用基因组DNA从两个IBS家族的受影响和未受影响的个体扩增。聚合酶链反应产物的直接测序揭示了高度保守的螺旋终止基序中的点突变，产生蛋白质序列改变LLEGEE-LLEGKE。在一个五代亲属的所有受影响成员中发现了这种突变，并且在第二个无关家族的散发病例中也发现了这种突变。在未受影响的个体中未观察到突变。该突变破坏了MnlI限制性位点，其允许通过K2 e PCR产物的限制性片段分析从50个未受影响的无关个体的群体中排除该突变。这是第六个角蛋白基因被发现参与遗传性表皮疾病。
Ichthyosis bullosa of Siemens (IBS) is a congenital bullous ichthyosis without erythroderma. In contrast to bullous congenital ichthyosiform erythroderma (BCIE), there is a relatively mild involvement of the skin and epidermolytic hyperkeratosis (EHK) is restricted to the upper suprabasal layers of the epidermis. Tonofilament aggregation was observed by EM in suprabasal cells from affected patients in the two families under study, indicative of a keratin abnormality. Keratin 2e is a differentiation specific type II keratin expressed suprabasally in the epidermis. Part of the K2e gene was amplified by polymerase chain reaction using genomic DNA from affected and unaffected individuals from two IBS families. Direct sequencing of polymerase chain reaction products revealed a point mutation in the highly conserved helix termination motif, producing the protein sequence change LLEGEE-LLEGKE. This mutation was found in all affected members of a five-generation kindred and also in a sporadic case in a second unrelated family. No mutation was seen in unaffected individuals. The mutation destroys a MnlI restriction site, which allowed exclusion of the mutation from a population of 50 unaffected unrelated individuals by restriction fragment analysis of K2e PCR products. This is the sixth keratin gene found to be involved in an inherited epidermal disorder.