Increased pachyonychia congenita severity in patients with concurrent keratin and filaggrin mutations
Increased pachyonychia congenita severity in patients with concurrent keratin and filaggrin mutations
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DOI：
10.1111/j.1365-2133.2009.09471.x
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发表时间：
2009-12-01
影响因子：
10.3
通讯作者：
Schmuth, M.
中科院分区：
文献类型：
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作者：
Gruber, R.;Wilson, N. J.;Schmuth, M.
先天性甲肥厚症（Pachyonychia congenita，PC）是一种罕见的常染色体显性角蛋白疾病，由角蛋白基因KRT 6A/B、KRT 16或KRT 17突变引起，以疼痛性足底角化病和肥大性甲营养不良为特征。丝聚蛋白（FLG）基因的功能缺失突变是最常见的角化皮肤病，寻常鱼鳞病（IV）的基础，其表现为全身鳞屑，也与特应性皮炎相关。最近，FLG突变已被报道增加X连锁鱼鳞病和斑秃的表型严重程度。我们报告了一个亲子三人组，其中母亲和儿子有PC和父亲有IV。母亲和儿子都是KRT 16突变p.Leu132Pro的携带者。儿子比他的母亲受到更严重的影响，此外还携带从父亲遗传的杂合FLG突变p.R2447X。这一观察结果表明，KRT 16和FLG突变的共同遗传可能会加重PC表型，FLG可以作为PC的遗传修饰剂。
P>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.