Title: Novel ADAR1 mutations including single amino acid deletion in the deaminase domain underly dyschromatosis symmetrica hereditaria
Abstract: Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary genodermatosis of autosomal dominant inheritance. It is characterized by hyperpigmented and hypopigmented macules on the dorsal hands and feet. Previous work has shown that a heterozygous ADAR1 mutation of the RNA-editing enzyme of adenosine deaminase acting on the RNA 1 (ADAR1) gene causes DSH, although the pathomechanism has not been clarified yet. In the present study, we identified two novel heterozygous ADAR1 mutations, one frameshift mutation c.536insC which results in p.Leu179fsX217 and the single amino acid deletion c.2615-7delTCA which results in p.Ile873del. Both patients were familial cases and had typical skin manifestation without any complication. p.Leu179fsX217 is on exon 2 of 15 exons and the mutation on this site would initiate nonsense-mediated mRNA decay, resulting in abolished ADAR1 protein product from the mutant allele. The novel three-nucleotide deletion c.2615-7delTCA is an in-frame mutation that leads to a single amino acid deletion: p.Ile873del. As far as we know, there are no previous reports of single amino acid deletions in ADAR1. The isoleucine residue at the position 873 is on the N-terminal portion of the deaminase domain. With respect to missense mutations, 45 such mutations have been reported in DSH so far; interestingly, the altered amino acids are all within the deaminase domain, suggesting that this domain is critical for enzyme function. The results of the present study further support the idea that the deaminase domain is important for intact ADAR1 function. It is particularly noteworthy that findings for the present DSH family with p.Ile873del clearly indicate that the isoleucine residue at the position 873 is essential for proper ADAR1 function. JSID AbstractsJournal of Dermatological ScienceVol. 69Issue 2Preview Full-Text PDF
Publication Year: 2013
Publication Date: 2013-02-01
Language: en
Type: article
Indexed In: ['crossref']
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Cited By Count: 1
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