Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Clin Exp Dermatol. 2013 Mar;38(2):189-92: quiz 192. doi: 10.1111/ced.12059. Epub 2013 Feb 9.
Epidermolytic palmoplantar keratoderma (EPPK) is caused by mutations in KRT9 and less often, KRT1. All known mutations in KRT9 have been found in regions of the gene encoding the conserved central α-helix rod domain. In the present study, we investigated the molecular basis of EPPK in a patient of Ashkenazi Jewish origin. The patient was found to carry a novel missense mutation in KRT9, resulting in the substitution of a poorly conserved leucine for valine at position 11 of the amino acid sequence. Despite its unusual location, the mutation was shown to be pathogenic through activation of a cryptic donor splice site, resulting in the deletion of 162 amino acids. The present data indicate the need to screen keratin genes in their entirety, as mutations altering domains of lesser functional importance may exert their deleterious effect at the transcriptional level.
表皮松解性掌跖角化症 (EPPK) 是由 KRT9 基因突变引起的，较少情况下是由 KRT1 基因突变引起的。所有已知的 KRT9 基因突变都发生在编码保守中央α-螺旋杆状结构域的基因区域。在本研究中，我们研究了一位阿什肯纳兹犹太裔起源的 EPPK 患者的分子基础。发现该患者携带 KRT9 的一种新的错义突变，导致第 11 位氨基酸序列中保守性较差的亮氨酸被缬氨酸取代。尽管突变位置不常见，但通过激活隐性供体位点剪接，导致 162 个氨基酸缺失，证明该突变是致病性的。本数据表明需要对整个角蛋白基因进行筛选，因为改变功能重要性较小的结构域的突变可能会在转录水平上产生有害影响。
