Arin M J, Longley M A, Anton-Lamprecht I, Kurze G, Huber M, Hohl D, Rothnagel J A, Roop D R
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
J Invest Dermatol. 1999 Apr;112(4):506-8. doi: 10.1046/j.1523-1747.1999.00557.x.
Epidermolytic hyperkeratosis is characterized by tonofilament clumping, cytolysis, and blister formation in suprabasal keratinocytes. It has been shown that the tonofilament aggregates in these areas are composed of keratin 1 (K1) and keratin 10 (K10), and several K1 and K10 point mutations have been identified as the molecular basis of epidermolytic hyperkeratosis. In this report we identify a novel, single base pair substitution resulting in an amino acid exchange from tyrosine to serine at residue 14 within the conserved 1A region of K10 (Y14S). This A to C transversion in codon 160 was only present in the affected individual and was associated with a very severe disease phenotype. Our observations are in agreement with previous reports documenting that this tyrosine residue, located at the beginning of the rod domain of type I keratins, is particularly sensitive to amino acid substitutions, and that alterations in this residue can have deleterious effects on filament assembly and stability.
表皮松解性角化过度的特征是基底上层角质形成细胞中张力丝聚集、细胞溶解和水疱形成。研究表明，这些区域的张力丝聚集体由角蛋白1（K1）和角蛋白10（K10）组成，并且已鉴定出几种K1和K10点突变是表皮松解性角化过度的分子基础。在本报告中，我们鉴定出一种新的单碱基对替换，该替换导致K10保守1A区域内第14位残基处的氨基酸从酪氨酸变为丝氨酸（Y14S）。密码子160处的这种A到C的颠换仅存在于受影响的个体中，并且与非常严重的疾病表型相关。我们的观察结果与先前的报告一致，这些报告记录了位于I型角蛋白杆状结构域起始处的这个酪氨酸残基对氨基酸替换特别敏感，并且该残基的改变可能对丝状体组装和稳定性产生有害影响。
