Hennies H C, Küster W, Mischke D, Reis A
Institute of Human Genetics, Free University Berlin, Germany.
Hum Mol Genet. 1995 Jun;4(6):1015-20. doi: 10.1093/hmg/4.6.1015.
Palmoplantar keratoderma is a frequent hereditary disorder of keratinization in humans. Various clinically, histopathologically and genetically distinct phenotypes can be diagnosed. Recently, mutations in the keratin genes have been identified in palmoplantar keratoderma: mutations in the keratin 9 gene causing the epidermolytic form, and mutations in the keratin 1 gene in a non-epidermolytic form. We have now investigated a family with the striated form of palmoplantar keratoderma (type Brünauer-Fuhs-Siemens) for linkage to either the type II keratin gene cluster on chromosome 12q or the type I keratin gene cluster on chromosome 17q. After excluding both type I and type II keratin genes we have mapped a locus for this form of palmoplantar keratoderma to chromosome 18q12 with a maximum two-point lod score of 3.3 at theta = 0.00 at D18S536. A cluster of desmosomal cadherin genes has been mapped to this region making them good candidates for this form of PPK. These findings indicate that hyperkeratosis of palms and soles is clinically as well as genetically heterogeneous.
掌跖角化病是人类常见的遗传性角化障碍。可诊断出各种临床、组织病理学和遗传学上不同的表型。最近，在掌跖角化病中已鉴定出角蛋白基因的突变：角蛋白9基因突变导致表皮松解型，角蛋白1基因突变导致非表皮松解型。我们现在研究了一个患有条纹状掌跖角化病（Brünauer-Fuhs-Siemens型）的家系，以确定其与12号染色体上的II型角蛋白基因簇或17号染色体上的I型角蛋白基因簇是否连锁。在排除I型和II型角蛋白基因后，我们将这种掌跖角化病的一个基因座定位到18号染色体q12，在D18S536位点，θ = 0.00时，最大两点连锁值为3.3。一组桥粒钙黏蛋白基因已定位到该区域，使其成为这种掌跖角化病类型的良好候选基因。这些发现表明，掌跖角化在临床和遗传上都是异质性的。
