A mutation in human keratin K6b produces a phenocopy of the K17 disorder pachyonychia congenita type 2
A mutation in human keratin K6b produces a phenocopy of the K17 disorder pachyonychia congenita type 2
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DOI：
10.1093/hmg/7.7.1143
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发表时间：
1998-07-01
影响因子：
3.5
通讯作者：
McLean, WHI
中科院分区：
文献类型：
--
作者：
Smith, FJD;Jonkman, MF;McLean, WHI
I型和II型角蛋白形成了异质聚合的中间丝细胞骨架，这是上皮细胞内的主要应力承载结构。先天性厚甲症（Pachyonychia congenita，PC）是一组常染色体显性遗传疾病，其最突出的表型是肥大性甲营养不良，伴有其他外胚层发育不良的特征。以前的研究表明，形成角蛋白表达对的K16或K6 a突变产生PC-1变体（MIM 184510），K17单独突变，一种未配对的辅助角蛋白，导致PC-2表型（MIM 184500），在这里，我们描述了一个PC-2家系，其中17 q上的K17位点被排除，并与12 q上的II型角蛋白位点连锁（Z（max））。3.31在theta = 0）。候选角蛋白的突变分析揭示了K6 b中首次报道的错义突变，这意味着该角蛋白是K17的先前未知的表达伴侣，类似于K6 a/K16对。通过原位杂交和免疫组织化学染色证实这些基因的GO表达。这些结果揭示了K6 b亚型在上皮生物学中迄今未知的作用，以及PC-2的遗传异质性。
Type I and type II keratins form the heteropolymeric intermediate filament cytoskeleton, which is the main stress-bearing structure within epithelial cells. Pachyonychia congenita (PC) is a group of autosomal dominant disorders whose most prominent phenotype is hypertrophic nail dystrophy accompanied by other features of ectodermal dysplasia, It has been shown previously that mutations in either K16 or K6a, which form a keratin expression pair, produce the PC-1 variant (MIM 184510), Mutations in K17 alone, an unpaired accessory keratin, result in the PC-2 phenotype (MIM 184500), Here, we describe a family with PC-2 in which the K17 locus on 17q was excluded and linkage to the type II keratin locus on 12q was obtained (Z(max) 3.31 at theta = 0). Mutation analysis of candidate keratins revealed the first reported missense mutation in K6b, implying that this keratin is the previously unknown expression partner of K17, analogous to the K6a/K16 pair. Go-expression of these genes was confirmed by in situ hybridization and immunohistochemical staining. These results reveal the hitherto unknown role of the K6b isoform in epithelial biology, as well as genetic heterogeneity in PC-2.