Park Joonhong, Jekarl Dong Wook, Kim Yonggoo, Kim Jiyeon, Kim Myungshin, Park Young Min
Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Catholic Genetic Laboratory Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.
J Dermatol. 2015 Sep;42(9):867-73. doi: 10.1111/1346-8138.12935. Epub 2015 May 21.
Filaggrin is essential for the development of the skin barrier. Mutations in the gene encoding filaggrin have been identified as major predisposing factors for atopic disorders. Molecular analysis of the FLG gene in this study showed nine null and one unclassified mutation in 13 of 81 Korean patients with atopic dermatitis (AD): five novel null mutations (i.e. p.S1405*, c.5671_5672delinsTA, p.W1947*, p.G2025* and p.E3070*); four reported null mutations (i.e. c.3321delA, p.S1515*, p.S3296* and p.K4022*); and one unclassified mutation (i.e. c.306delAAAGCACAG). These variants are nonsense, premature termination codon or in-frame deletion expected to cause loss-of-function of FLG. Genotype-phenotype correlation is not obvious in Korean AD patients with FLG null mutations. According to a review of the mutational spectra of the FLG gene in the Asian populations, FLG null mutations appeared to be unique in each population but some mutations such as p.R501*, c.3321delA, p.S1515*, p.S3296* and p.K4022* were commonly found in at least two of the selected Asian populations including Korean, Japanese, Chinese, Singaporean Chinese or Taiwanese. Further investigations on a larger group of Korean AD would be necessary to elucidate its clinical pathogenesis and mutational spectrum related to specific FLG null mutations for AD.
丝聚合蛋白对于皮肤屏障的发育至关重要。编码丝聚合蛋白的基因突变已被确定为特应性疾病的主要易感因素。本研究对FLG基因的分子分析显示，在81例韩国特应性皮炎（AD）患者中的13例中发现了9个无效突变和1个未分类突变：5个新的无效突变（即p.S1405*、c.5671_5672delinsTA、p.W1947*、p.G2025和p.E3070）；4个已报道的无效突变（即c.3321delA、p.S1515*、p.S3296和p.K4022）；以及1个未分类突变（即c.306delAAAGCACAG）。这些变异为无义突变、过早终止密码子或框内缺失，预计会导致FLG功能丧失。在携带FLG无效突变的韩国AD患者中，基因型与表型的相关性并不明显。根据对亚洲人群FLG基因突变谱的综述，FLG无效突变在每个群体中似乎都是独特的，但一些突变如p.R501*、c.3321delA、p.S1515*、p.S3296和p.K4022在至少两个选定的亚洲人群中普遍存在，包括韩国人、日本人、中国人、新加坡华人或台湾人。有必要对更多韩国AD患者进行进一步研究，以阐明其临床发病机制以及与AD特定FLG无效突变相关的突变谱。
