Four novel mutations of the ADAR1 gene in dyschromatosis symmetrica hereditaria

Murata, Ichidai; Hozumi, Yasukazu; Kawaguchi, Masakazu; Katagiri, Yoshiyuki; Yasumoto, Shinichiro; Kubo, Yoshiaki; Fujimoto, Wataru; Horikawa, Tsuyoshi; Kondo, Taisuke; Kono, Michihiro; Tomita, Yasushi; Suzuki, Tamio

doi:10.1016/j.jdermsci.2008.07.011

Cited by 14 publications

(10 citation statements)

References 10 publications

(15 reference statements)

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“…Both of them were missense mutations, suggesting the replacements of serine 915 by phenylalanine and arginine 1155 by tryptophan, respectively [8,9]. …”

Section: Resultsmentioning

confidence: 99%

“…In addition, Figure 4 suggested that the mutations c.556C > T and c.1065_1068delGACA might reduce the expression of mutant proteins and we speculated that the nonsense-mediated mRNA decay (NMD) might be one of the possibilities. For the missense mutations c.3001C > T (p.Arg1001Cys), c.2744C > T (p.Ser915Phe) and c.3463C > T (p.Arg1155Trp), the transitions of nucleotides change codons in the highly conserved region of ADEAMc domain, which possibly alter the activity of ADAR1 directly, or by disturbing the formation of wild-type ADAR1 homodimers [9]. In family 5, the aberrant splicing decreased approximately half ADAR1 mRNA level, potentially caused by NMD, supporting that haploinsufficiency of ADAR1 produces DSH [5,9].…”

Section: Discussionmentioning

confidence: 99%

“…For the missense mutations c.3001C > T (p.Arg1001Cys), c.2744C > T (p.Ser915Phe) and c.3463C > T (p.Arg1155Trp), the transitions of nucleotides change codons in the highly conserved region of ADEAMc domain, which possibly alter the activity of ADAR1 directly, or by disturbing the formation of wild-type ADAR1 homodimers [9]. In family 5, the aberrant splicing decreased approximately half ADAR1 mRNA level, potentially caused by NMD, supporting that haploinsufficiency of ADAR1 produces DSH [5,9]. In addition, we compared the clinical features with the mutations indentified in all the families but failed to find any clear relationship between phenotypes and genotypes as other groups have reported [2,13].…”

Section: Discussionmentioning

confidence: 99%

“…Although ADAR1 expressed ubiquitously in mammalian tissues and playing various roles such as viral host defense, embryonic development, tumor growth and miRNA processing [22-25], only a few its target genes including the neurotransmitter receptors in the central nervous system and the hepatitis virus antigen in the liver are identified [9]. Therefore, mutations in the ADAR1 might associate with neurological dysfunction such as dystonia and mental deterioration [26].…”

Section: Discussionmentioning

confidence: 99%

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Five novel mutations in the ADAR1 gene associated with dyschromatosis symmetrica hereditaria

Liu

Wang

et al. 2014

BMC Med Genet

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BackgroundDyschromatosis symmetrica hereditaria (DSH) is an autosomal dominantly inherited skin disease associated with mutations of ADAR1, the gene that encodes a double-stranded RNA-specific adenosine deaminase. The purpose of this study was to investigate the potential mutations in ADAR1 in seven Chinese families with DSH.MethodsAll the coding exons including adjacent intronic as well as 5′ and 3′ untranslated region (UTR) of ADAR1 were screened by direct sequencing. Moreover, quantitative reverse-transcription polymerase chain (qRT-PCR) and Western blot were applied to determine the pathogenic effects associated with the mutations.ResultsMolecular genetic investigations detected five novel mutations (c.556C > T, c.3001C > T, c.1936_1937insTG, c.1065_1068delGACA and c.1601G > A resulting in p.Gln186X, p.Arg1001Cys, p.Phe646LeufsX16, p.Asp357ArgfsX47 and p.Gly471AspfsX30 protein changes, respectively) as well as two previously reported (c.2744C > T and c.3463C > T causing p.Ser915Phe and p.Arg1155Trp protein changes, respectively). Among them, we found that the substitution c.1601G > A at the last nucleotide of exon 2 compromised the recognition of the splice donor site of intron 2, inducing an aberrant transcript with 190-bp deletion in exon 2 and causing an approximately 50% reduction of ADAR1 mRNA level in affected individual. In addition, consistent with the predicted results, the expression patterns of other novel mutations were detected by Western blot.ConclusionWe identified five novel and two recurrent mutations of the ADAR1 gene in seven Chinese families with DSH and investigated potential effects of the novel mutations in this study. Our study expands the database on mutations of ADAR1 and for the first time, demonstrates the importance of exonic nucleotides at exon-intron junctions for ADAR1 splicing.

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“…Both of them were missense mutations, suggesting the replacements of serine 915 by phenylalanine and arginine 1155 by tryptophan, respectively [8,9]. …”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Five novel mutations in the ADAR1 gene associated with dyschromatosis symmetrica hereditaria

Liu

Wang

et al. 2014

BMC Med Genet

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“…Interestingly nonsense mutations that encode proteins similar to those in the knockout mice have been reported in DSH patients, such as R328X [10] or Y989X [62]. Notably, DSH patients are heterozygous for the ADAR1 gene mutation that is inherited as a dominant trait.…”

Section: Dsh Murine Modelsmentioning

confidence: 99%

Dyschromatosis Symmetrica Hereditaria and RNA Editing Enzyme

Kono¹,

Akiyama²

2013

Current Genetics in Dermatology

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Two new mutations of the ADAR1 gene associated with dyschromatosis symmetrica hereditaria

Sun

et al. 2010

Arch Dermatol Res

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Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary genodermatosis of autosomal dominant inheritance characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the dorsal aspects of the hands and feet. Genetic studies have identified mutations in ADAR1 gene to be responsible for this disorder. We detected two mutations in two families with DSH, which include a heterozygous g-->a transversion at the first base of the 3'-acceptor splice site of intron 5 (c. 2080-1g>a, IVS5-1g>a) and a transition c.3076C>T. IVS5-1g>a should prevent proper splicing of the transcript while c.3076C>T leading to a missense mutation p.R1026W of the ADAR1 gene. Our study suggests that splice site mutation IVS5-1g>a and missense mutation p.R1026W are new mutations of ADAR1 gene, which should be useful in genetic counseling and prenatal diagnosis for the affected families and expanding the database on ADAR1 gene mutations in DSH.

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Four novel mutations of the ADAR1 gene in dyschromatosis symmetrica hereditaria

Cited by 14 publications

References 10 publications

Five novel mutations in the ADAR1 gene associated with dyschromatosis symmetrica hereditaria

Five novel mutations in the ADAR1 gene associated with dyschromatosis symmetrica hereditaria

Dyschromatosis Symmetrica Hereditaria and RNA Editing Enzyme

Two new mutations of the ADAR1 gene associated with dyschromatosis symmetrica hereditaria

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