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Previous Volume 331:1408-1415 November 24, 1994 Number 21 Next

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ABSTRACT

Background 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.

Methods 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.

Results 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.

Conclusions 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.

Source Information

From the Departments of Pediatrics and Dermatology, Northwestern University Medical School, Chicago (A.S.P.); the Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago (A.J.S., Y.-M.C., Q.-C.Y., E.H., E.F.); and the Department of Dermatology, University of Milan, Milan, Italy (G.T.).

Address reprint requests to Dr. Paller at the Division of Dermatology, #107, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614.

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