Dataset Information

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

ABSTRACT: BACKGROUND: Dyschromatosis 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. METHODS: All 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. RESULTS: Molecular 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. CONCLUSION: We 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.

SUBMITTER: Liu Q

PROVIDER: S-EPMC4105233 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Liu Qi Q Wang Zhen Z Wu Yuhong Y Cao Lihua L Tang Qingzhu Q Xing Xuesha X Ma Hongwei H Zhang Shifa S Luo Yang Y

BMC medical genetics 20140620

<h4>Background</h4>Dyschromatosis 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.<h4>Methods</h4>All the coding exons including adjacent intronic as well as 5' and 3' untranslated region (UTR) of ADAR1 were screened by direct sequencing. Moreove ...[more]

PMID: 24950769

Similar Datasets

Project description:ObjectiveDyschromatosis universalis hereditaria (DUH) is a rare heterogeneous pigmentary genodermatosis, which was first described in 1933. The genetic cause has recently been discovered by the discovery of mutations in ABCB6. Here we investigated a Chinese family with typical features of autosomal dominant DUH and 3 unrelated patients with sporadic DUH.MethodsSkin tissues were obtained from the proband, of this family and the 3 sporadic patients. Histopathological examination and immunohistochemical analysis of ABCB6 were performed. Peripheral blood DNA samples were obtained from 21 affected, 14 unaffected, 11 spouses in the family and the 3 sporadic patients. A genome-wide linkage scan for the family was carried out to localize the causative gene. Exome sequencing was performed from 3 affected and 1 unaffected in the family. Sanger sequencing of ABCB6 was further used to identify the causative gene for all samples obtained from available family members, the 3 sporadic patients and a panel of 455 ethnically-matched normal Chinese individuals.ResultsHistopathological analysis showed melanocytes in normal control's skin tissue and the hyperpigmented area contained more melanized, mature melanosomes than those within the hypopigmented areas. Empty immature melanosomes were found in the hypopigmented melanocytes. Parametric multipoint linkage analysis produced a HLOD score of 4.68, with markers on chromosome 2q35-q37.2. A missense mutation (c.1663 C>A, p.Gln555Lys) in ABCB6 was identified in this family by exome and Sanger sequencing. The mutation perfectly cosegregated with the skin phenotype. An additional mutation (g.776 delC, c.459 delC) in ABCB6 was found in an unrelated sporadic patient. No mutation in ABCB6 was discovered in the other two sporadic patients. Neither of the two mutations was present in the 455 controls. Melanocytes showed positive immunoreactivity to ABCB6.ConclusionOur data add new variants to the repertoire of ABCB6 mutations with DUH.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets