Paller A S, Syder A J, Chan Y M, Yu Q C, Hutton E, Tadini G, Fuchs E
Department of Pediatrics, Northwestern University Medical School, Chicago, IL.
N Engl J Med. 1994 Nov 24;331(21):1408-15. doi: 10.1056/NEJM199411243312103.
Many skin disorders are characterized by a mosaic pattern, often with alternating stripes of affected and unaffected skin that follow the lines of Blaschko. These nonrandom patterns may be caused by a postzygotic mutation during embryogenesis. We studied the genetic basis of one such disorder, epidermal nevus of the epidermolytic hyperkeratotic type. Epidermolytic hyperkeratosis is an autosomal dominant blistering skin disease arising from mutations in the genes for keratin (K) 1 and 10. The offspring of patients with epidermal nevi may have generalized epidermolytic hyperkeratosis.
We studied the K1 and K10 genes in blood and in the keratinocytes and fibroblasts of lesional and nonlesional skin from three patients with epidermal nevi and four of their offspring with epidermolytic hyperkeratosis.
In the patients with epidermal nevi, point mutations in 50 percent of the K10 alleles of epidermal cells were found in keratinocytes from lesional skin; no mutations were detected in normal skin. This mutation was absent or underrepresented in blood and skin fibroblasts. In the offspring with epidermolytic hyperkeratosis, the same mutations as those in the parents were found in 50 percent of the K10 alleles from all cell types examined.
Epidermal nevus of the epidermolytic hyperkeratotic type is a mosaic genetic disorder of suprabasal keratin. The correlation of mutations in the K10 gene with lesional skin and the correlation of the normal gene with normal skin provide evidence that genetic mosaicism can cause clinical mosaicism.
许多皮肤疾病具有镶嵌模式，通常有沿布拉斯科线交替出现的受累皮肤和未受累皮肤条纹。这些非随机模式可能由胚胎发育过程中的合子后突变引起。我们研究了一种此类疾病——表皮松解性角化过度型表皮痣的遗传基础。表皮松解性角化过度是一种常染色体显性遗传性水疱性皮肤病，由角蛋白（K）1和10基因的突变引起。表皮痣患者的后代可能患有全身性表皮松解性角化过度。
我们研究了3例表皮痣患者及其4例患有表皮松解性角化过度的后代的血液、皮损和非皮损皮肤的角质形成细胞及成纤维细胞中的K1和K10基因。
在表皮痣患者中，在皮损皮肤的角质形成细胞中发现50%的表皮细胞K10等位基因存在点突变；正常皮肤中未检测到突变。血液和成纤维细胞中不存在该突变或该突变表达不足。在患有表皮松解性角化过度的后代中，在所检测的所有细胞类型中，50%的K10等位基因存在与父母相同的突变。
表皮松解性角化过度型表皮痣是一种基底层以上角质形成细胞的镶嵌性遗传病。K10基因突变与皮损皮肤的相关性以及正常基因与正常皮肤的相关性提供了遗传镶嵌性可导致临床镶嵌性的证据。
