Novel mutations of the ADAR1 gene in two Chinese families with dyschromatosis symmetrica hereditaria

Abstract

CorrespondenceNovel mutations of the ADAR1 gene in two Chinese families with dyschromatosis symmetrica hereditaria Dyschromatosis symmetrica hereditaria (DSH; MIM 127400) is an autosomal dominant genodermatosis characterized by intermingled hyper-and hypopigmented macules on the dorsal aspect of the distal extremities. The pathogenic mutations of DSH have been identified in adenosine deaminase acting on RNA 1 (ADAR1) gene. 1 In this study, we have investigated two families from Liaoning, China, with typical DSH features and explored the effect of mutations.Family 1, a four-generation pedigree containing eight affected and 19 unaffected individuals, was consistent with an autosomal dominant mode of inheritance (Fig. 1a). The proband, a 27-year-old man, had a mixture of hyperpigmented and hypopigmented macules on the dorsal aspects of his extremities, face, knees, and back (Fig. 1b). Other affected family members only had similar macules on their extremities and face. In family 2, a sporadic case has been identified. The patient has developed small freckle-like pigmented macules on the face and typical symptoms on the dorsal extremities (Fig. 2a). Figure 1 Mutations of DSH family 1. (a) Four-generation family, which included eight patients. (b)Proband has a mixture of hyperpigmented and hypopigmented macules on his body and was asymptomatic. (c) Novel A?T splice mutation (IVS12-2 A>T), which was discovered in all patients from the family. (d) As confirmed by RT-PCR, the abnormally spliced RNA lacks 183 nucleotides in the mature RNA. On an electrophoresis gel, the normal splicing produced a single 670 bp band, while the abnormal splicing has produced two bands (670 bp and 487 bp, respectively). (e) Sequencing of RT-PCR product has confirmed that the brachytmema sequence lacks exon 12