Covello S P, Smith F J, Sillevis Smitt J H, Paller A S, Munro C S, Jonkman M F, Uitto J, McLean W H
Epithelial Genetics Group, Department of Dermatology and Cutaneous Biology, Jefferson Medical College, 233 South 10th Street, Philadelphia, PA 19107, USA.
Br J Dermatol. 1998 Sep;139(3):475-80. doi: 10.1046/j.1365-2133.1998.02413.x.
Pachyonychia congenita type 2 (PC-2; Jackson-Lawler syndrome) is an autosomal dominant disorder characterized by hypertrophic nail dystrophy, mild focal keratoderma, multiple pilosebaceous cysts and other features of ectodermal dysplasia. Keratin 17 (K17) is a differentiation-specific keratin expressed in the nail bed, hair follicle, sebaceous gland and other epidermal appendages. Previously, we have demonstrated that PC-2 is caused by mutations in K17 and that similar mutations in this gene can present as steatocystoma multiplex with little or no nail dystrophy. Here, we describe three unrelated kindreds carrying K17 mutations. Two of these families have identical missense mutations (R94C) in the 1A domain of K17. However, while affected members of one kindred have the classical features of PC-2, affected persons in the other family have the steatocystoma multiplex phenotype. In a third family with PC-2, mutation N92S was detected, bringing the total number of distinct mutations reported in K17 thus far to 11. These results demonstrate that K17 mutations commonly underlie both PC-2 and steatocystoma multiplex and that the alternate phenotypes which arise from these genetic lesions in K17 are independent of the specific mutation involved.
2型先天性厚甲症（PC - 2；杰克逊 - 劳勒综合征）是一种常染色体显性疾病，其特征为肥厚性甲营养不良、轻度局限性角化病、多发性皮脂腺囊肿以及其他外胚层发育异常的特征。角蛋白17（K17）是一种在甲床、毛囊、皮脂腺和其他表皮附属器中表达的分化特异性角蛋白。此前，我们已经证明PC - 2是由K17基因突变引起的，并且该基因中的类似突变可表现为多发性皮脂囊肿，伴有很少或没有甲营养不良。在此，我们描述了三个携带K17突变的无关家族。其中两个家族在K17的1A结构域中有相同的错义突变（R94C）。然而，一个家族的受累成员具有PC - 2的典型特征，而另一个家族的受累者具有多发性皮脂囊肿表型。在第三个患有PC - 2的家族中，检测到N92S突变，使迄今为止报道的K17中不同突变的总数达到11个。这些结果表明，K17突变通常是PC - 2和多发性皮脂囊肿的共同基础，并且由K17中的这些基因损伤产生的交替表型与所涉及的特定突变无关。
