Department of Dermatology, Innsbruck Medical University, Innsbruck, Austria.
Br J Dermatol. 2009 Dec;161(6):1391-5. doi: 10.1111/j.1365-2133.2009.09471.x. Epub 2009 Sep 28.
Pachyonychia congenita (PC), a rare autosomal-dominant keratin disorder caused by mutations in keratin genes KRT6A/B, KRT16 or KRT17, is characterized by painful plantar keratoderma and hypertrophic nail dystrophy. Loss-of-function mutations in the filaggrin (FLG) gene underlie the most prevalent skin disorder of cornification, ichthyosis vulgaris (IV), which presents with generalized scaling and is also associated with atopic dermatitis. Recently, FLG mutations have been reported to increase phenotype severity of X-linked ichthyosis and alopecia areata. We report a parent-child trio in which the mother and the son have PC and the father has IV. Both the mother and the son are carriers for the KRT16 mutation p.Leu132Pro. The son, who is much more severely affected than his mother, in addition carries the heterozygous FLG mutation p.R2447X, which was inherited from the father. This observation suggests that coinheritance of mutations in KRT16 and FLG may aggravate the PC phenotype and that FLG could serve as a genetic modifier in PC.
先天性厚甲症（PC）是一种罕见的常染色体显性遗传角化病，由角蛋白基因 KRT6A/B、KRT16 或 KRT17 的突变引起，其特征为足底角化过度性疼痛和增厚性指甲营养不良。丝聚蛋白（FLG）基因突变导致最常见的角化不全性皮肤病——寻常型鱼鳞病（IV），表现为全身性鳞屑，也与特应性皮炎有关。最近，FLG 突变被报道会增加 X 连锁鱼鳞病和斑秃的表型严重程度。我们报告了一个母子三人的病例，母亲和儿子患有 PC，父亲患有 IV。母亲和儿子均为 KRT16 突变 p.Leu132Pro 的携带者。与母亲相比，儿子的病情严重得多，他还携带了来自父亲的杂合性 FLG 突变 p.R2447X。这一观察结果表明，KRT16 和 FLG 突变的共同遗传可能会加重 PC 的表型，而 FLG 可能是 PC 的遗传修饰因子。
