Six novel mutations of the ADAR1 gene in patients with dyschromatosis symmetrica hereditaria: Histological observation and comparison of genotypes and clinical phenotypes
Article first published online: 10 JUL 2008
© 2008 Japanese Dermatological Association
The Journal of Dermatology
Volume 35, Issue 7, pages 395–406, July 2008
How to Cite
KONDO, T., SUZUKI, T., MITSUHASHI, Y., ITO, S., KONO, M., KOMINE, M., AKITA, H. and TOMITA, Y. (2008), Six novel mutations of the ADAR1 gene in patients with dyschromatosis symmetrica hereditaria: Histological observation and comparison of genotypes and clinical phenotypes. The Journal of Dermatology, 35: 395–406. doi: 10.1111/j.1346-8138.2008.00493.x
- Issue published online: 10 JUL 2008
- Article first published online: 10 JUL 2008
- Received 20 November 2007; accepted 29 February 2008.
- dyschromatosis symmetrica hereditaria;
- electron microscopy;
- novel mutation
Dyschromatosis symmetrica hereditaria (DSH), is a pigmentary genodermatosis of autosomal dominant inheritance. Since we clarified that the disease is caused by a mutation of the adenosine deaminase acting on the RNA 1 gene (ADAR1) in 2003, the molecular pathogenesis of a peculiar clinical feature of the disease has been expected to be clarified. We examined five familial cases and one sporadic case of Japanese families with DSH. The mutation analyses were done with single-strand conformation polymorphism/heteroduplex (SSCP/HD) analysis and direct sequencing of ADAR1. The DNA analysis of each patient revealed one missense mutation (p.F1091S), two nonsense mutations (p.C893X, p.S581X) and three frame-shift mutations (p.E498fsX517, p.F1091fsX1092, p.L855fsX856). Visual and electron microscopic findings showed abundant melanin pigment deposited all over the basal layer, and enlarged melanocytes with long dendrites located in the pigmented lesions with small or immature melanosomes scattered sparsely in the cytoplasm, but in the adjacent keratinocytes many small melanosomes were singly dispersed or aggregated. The hypopigmented areas showed little melanin deposition and reduced numbers of melanocytes in which much degenerative cytoplasmic vacuole formation could be observed by electron microscopy. Herein, we report six cases of DSH with six novel mutations. The variety of their clinical phenotypes even in the pedigree may suggest the presence of factors other than the ADAR1 gene influencing the extent of the clinical skin lesion. Microscopic findings suggest that the clinical appearance must have developed directly by melanocyte variations mainly induced by the ADAR1 gene mutations.