State Key Laboratory of Medical Genetics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Clin Exp Dermatol. 2012 Mar;37(2):177-80. doi: 10.1111/j.1365-2230.2011.04229.x. Epub 2012 Feb 2.
Loss-of-function mutations in the gene encoding filaggrin (FLG) can cause the semidominant keratinizing disorder ichthyosis vulgaris (OMIM 146700). To identify FLG mutations in three Chinese pedigrees with ichthyosis vulgaris, we sequenced the entire coding region of FLG in the proband of each pedigree. We found two novel FLG null mutations (c.477-478insA and c.6218-6219delAA) and a known mutation (c.3321delA). Both novel mutations were identified in the proband of pedigree 1; c.477-478insA was inherited from the proband's father, and the other was a de novo mutation. Neither of these two mutations was found in 200 unrelated controls. These findings extend the spectrum of functional FLG variants possibly causing ichthyosis vulgaris. Interestingly, the proband of pedigree 1 was compound heterozygous for these mutations, but had a mild phenotype, suggesting that an incomplete penetrance factor and perhaps other unknown factors may be involved in the pathogenesis of ichthyosis vulgaris.
编码丝聚蛋白（FLG）的基因突变可导致半显性角化障碍寻常型鱼鳞病（OMIM 146700）。为了鉴定三个中国寻常型鱼鳞病家系中的 FLG 突变，我们对每个家系的先证者进行了 FLG 全长编码区的测序。我们发现了两个新的 FLG 无义突变（c.477-478insA 和 c.6218-6219delAA）和一个已知的突变（c.3321delA）。两个新突变均存在于家系 1的先证者中；c.477-478insA 来自先证者的父亲，另一个为新生突变。这两个突变在 200 名无关对照中均未发现。这些发现扩展了可能导致寻常型鱼鳞病的功能性 FLG 变异谱。有趣的是，家系 1 的先证者为这两种突变的复合杂合子，但表型较轻，提示不完全外显率因素和其他未知因素可能参与了寻常型鱼鳞病的发病机制。
