Identification of two novel splice mutations of the ADAR1 gene in two Chinese families with dyschromatosis symmetrica hereditaria

Abstract

Dyschromatosis symmetrica hereditaria (DSH) is a rare, autosomal dominant dermatosis, characterized by a mixture of hyperpigmented and hypopigmented macules on the dorsa of the hands and feet. The DSH locus has been mapped to chromosome 1q21, and in 2003, pathogenic mutations were identified in the ADAR1 (adenosine deaminase acting on RNA1) gene. In this study, we performed mutation detection of the ADAR1 gene in two Chinese families with DSH. PCR and direct sequencing of the ADAR1 gene were used to identify and confirm the mutations in the two families. Furthermore, we analysed the RNA transcripts by reverse transcriptase (RT)-PCR. Two aberrant splice products were confirmed with RT-PCR and DNA direct sequence analysis. These novel findings further extend our understanding of the role of ADAR1 in DSH.

Knockdown of Adenosine Deaminase 1 Acting on dsRNA Inhibits Expression of Proopiomelanocortin in HaCaT Cells

“…For this reason, it can be assumed that DSH is caused by the dysfunctional regulation of melanogenesis in skin cells, and the disease gene ADAR1 might be involved in regulating melanogenesis. In fact, the ADAR1 gene has been known to play an important role in the regulatory functions of epidermal skin cells [10]. In the present study, our results clearly demonstrate that ADAR1 knockdown inhibits POMC expression in HaCaT cells.…”

“…No pigmentation abnormality is detected in the limbs of ADAR1+/− mice [10]. Recently, the ADAR1 gene has been shown to play key, direct roles in the regulatory functions of epidermal skin cells [10]. Hence, it will be interesting to see if an ADAR1-specific RNA editing target(s) will emerge in the future that can explain the observed DSH phenotype and disease mechanism.…”

“…In mice heterozygous for an ADAR1 null mutation, no phenotype is discernible, whereas homozygous ADAR1 knock-out animals die during early embryogenesis [8], [9]. No pigmentation abnormality is detected in the limbs of ADAR1+/− mice [10]. Recently, the ADAR1 gene has been shown to play key, direct roles in the regulatory functions of epidermal skin cells [10].…”

Prevalence of AIP mutations in a series of Turkish acromegalic patients: are synonymous AIP mutations relevant?

“…An effect of synonymous codon usage on gene expression is supported by the detection of epistatic interactions between nucleotides that are important in maintaining pre-mRNA/mRNA secondary structures [33][34][35][36]. In addition, some synonymous changes in humans have been shown to cause genetic disorders by exon skipping [37,38]. As a result, synonymous mutations are thought to lead to decreased mRNA translation and decreased mRNA stability [39].…”

Mutations in the ADAR1 gene in 2 Chinese families with dyschromatosis symmetrica hereditaria

“…The predicted protein lacked 753 amino acids. To date, a total of 110 mutations in the ADAR1 gene have been reported (Li et al, 2010a,b;Murata et al, 2010;Wang et al, 2010;Dong et al, 2011;Liu et al, 2011;Liu et al, 2012), and 10 of them (9.09%), including the c.1420C>T mutation in exon 2 of ADAR1 described here, were recurrent (Table 1). Both the R1083C and R1155W mutations have been reported 3 times in 3 unrelated families.…”