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

Li, Chengrang; Xu, Xiaogang; Sun, Xinjun; Zong, Wenxia; Sheng, Nan; Bu, Jin; Li, Ming; Cui, Pangen

doi:10.1007/s00403-010-1037-4

Cited by 8 publications

(4 citation statements)

References 8 publications

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“…mapped the causative gene of DSH to 1q11‐1q21 and found that a novel mutation of a heterozygous nucleotide A→G at position 2879 in exon 10 of the DSRAD gene is involved in DSH . Subsequent research on dyspigmentation has demonstrated that the pathogenic genetic variant that causes DSH is localized to the DSRAD gene on chromosome 1q . Expanding Stuhrmann and Nuber's findings and our own previous work providing photographic evidence of dyschromatosis presenting as large hyperpigmented bodies on DUH‐affected individuals , we believe that we have discovered the first locus associated with autosomal‐dominant DUH, identifying SASH1 as the causative gene of autosomal‐dominant DUH.…”

Section: Discussionmentioning

confidence: 99%

A novel P53/POMC/Gαs/SASH1 autoregulatory feedback loop activates mutated SASH1 to cause pathologic hyperpigmentation

Zhou

Wei

Kuang

et al. 2016

J Cellular Molecular Medi

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Abstractp53‐Transcriptional‐regulated proteins interact with a large number of other signal transduction pathways in the cell, and a number of positive and negative autoregulatory feedback loops act upon the p53 response. P53 directly controls the POMC/α‐MSH productions induced by ultraviolet (UV) and is associated with UV‐independent pathological pigmentation. When identifying the causative gene of dyschromatosis universalis hereditaria (DUH), we found three mutations encoding amino acid substitutions in the gene SAM and SH3 domain containing 1 (SASH1), and SASH1 was associated with guanine nucleotide‐binding protein subunit‐alpha isoforms short (Gαs). However, the pathological gene and pathological mechanism of DUH remain unknown for about 90 years. We demonstrate that SASH1 is physiologically induced by p53 upon UV stimulation and SASH and p53 is reciprocally induced at physiological and pathophysiological conditions. SASH1 is regulated by a novel p53/POMC/α‐MSH/Gαs/SASH1 cascade to mediate melanogenesis. A novel p53/POMC/Gαs/SASH1 autoregulatory positive feedback loop is regulated by SASH1 mutations to induce pathological hyperpigmentation phenotype. Our study demonstrates that a novel p53/POMC/Gαs/SASH1 autoregulatory positive feedback loop is regulated by SASH1 mutations to induce pathological hyperpigmentation phenotype.

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Section: Discussionmentioning

confidence: 99%

A novel P53/POMC/Gαs/SASH1 autoregulatory feedback loop activates mutated SASH1 to cause pathologic hyperpigmentation

Zhou

Wei

Kuang

et al. 2016

J Cellular Molecular Medi

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“…Since the finding in 2003 that the ADAR1 gene is responsible for DSH, only seven mutations involving splice sites of this gene have been reported, [3][4][5][6] (Table 1), which is approximately 6.4% of the 110 mutations. [2][3][4][5][6][7][8][9][10] There are two main mechanisms of novel splicing induced by mutations. The first is skipping of the exon Figure 1 Clinical appearance of the proband in family 1.…”

Section: Reportmentioning

confidence: 99%

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

Liu

et al. 2011

Clinical and Experimental Dermatology

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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.

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“…The ADAR1 enzyme has two Z-alpha domains at exon 2, three double-stranded RNA binding domains at exons 2 to 7, and a putative deaminase domain (ADEAMc) corresponding to exons 9 to 14 (Li et al, 2010a). The deaminase domain, located in the codon from 886 to 1221 bp, represents approximately 27% of the length of the ADAR1 protein, (XuFeng et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

A novel insertion mutation in the ADAR1 gene of a Chinese family with dyschromatosis symmetrica hereditaria

Zhu¹,

Zhu²,

Zhou³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant pigmentary genodermatosis, characterized by a mixture of hyperpigmented and hypopigmented macules that are mainly present on the dorsal portions of the extremities. The DSH locus was mapped to chromosome 1q11-q12 and, subsequently, pathogenic mutations in the double-stranded RNA-specific adenosine deaminase (ADAR1) gene were identified. We performed a mutational analysis of the ADAR1 gene in a Chinese family that included three individuals affected with typical DSH phenotypes. Mutations within the entire coding region and the exon-intron boundaries of ADAR1 were detected and confirmed by polymerase chain reaction and direct sequencing, respectively. An insertion mutation within exon 12, c.3035_3036insC (p.P1012fsX1017), was identified in all family members affected by DSH, but not in the healthy members or 100 unrelated controls. This finding improves our understanding of the role of ADAR1 in DSH.

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

Cited by 8 publications

References 8 publications

A novel P53/POMC/Gαs/SASH1 autoregulatory feedback loop activates mutated SASH1 to cause pathologic hyperpigmentation

A novel P53/POMC/Gαs/SASH1 autoregulatory feedback loop activates mutated SASH1 to cause pathologic hyperpigmentation

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

A novel insertion mutation in the ADAR1 gene of a Chinese family with dyschromatosis symmetrica hereditaria

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