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Genetic spectrum of dyschromatosis symmetrica hereditaria in Chinese patients including a novel nonstop mutation in ADAR1 gene.

Zhang G, Shao M, Li Z, Gu Y, Du X, Wang X, Li M - BMC Med. Genet. (2016)

Bottom Line: In silico analysis proves that all the mutations reported here are pathogenic.This study is useful for functional studies of the protein and to define a diagnostic strategy for mutation screening of the ADAR1 gene.A three-generation family exhibiting phenotypic variability with a single germline ADAR1 mutation suggests that chilblain might aggravate the clinical phenotypes of DSH.

View Article: PubMed Central - PubMed

Affiliation: Department of Phototherapy at Shanghai Skin Disease Hospital & Institute of Photomedicine, Tongji University School of Medicine, 1278, Baode Road, Shanghai, 200443, China. zglamu@163.com.

ABSTRACT

Background: Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant cutaneous disorder caused by the mutations of adenosine deaminase acting on RNA1 (ADAR1) gene. We present a clinical and genetic study of seven unrelated families and two sporadic cases with DSH for mutations in the full coding sequence of ADAR1 gene.

Methods: ADAR1 gene was sequenced in seven unrelated families and two sporadic cases with DSH and 120 controls. Functional significance of the observed ADAR1 mutations was analyzed using PolyPhen 2, SIFT and DDIG-in.

Results: We describe six novel mutations of the ADAR1 gene in Chinese patients with DSH including a nonstop mutation p.Stop1227R, which was firstly reported in ADAR1 gene. In silico analysis proves that all the mutations reported here are pathogenic.

Conclusion: This study is useful for functional studies of the protein and to define a diagnostic strategy for mutation screening of the ADAR1 gene. A three-generation family exhibiting phenotypic variability with a single germline ADAR1 mutation suggests that chilblain might aggravate the clinical phenotypes of DSH.

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Mutations of the ADAR1 gene found in patients with dyschromatosis symmetrica hereditaria. a. c.1078C>T (p.R360X) mutation in family 4. b. c.1420C>T (p.R474X) mutation in family 6. c. c.2303G>A (p.W768X) mutation in Sporadic 1. d.c.3248G>A (p.R1083H) mutation in family 7. e.c.3089_3090delGA (p.R1030DfsX1036) mutation in family 1. f. c.2408delG (p.G803VfsX807) mutation in family 3. g. c.3439ins17 (p.D1147VfsX1184) mutation in family 5. h. a nonstop mutation TGA(Stop) CGA(Arg)=Stop1227R in family 2
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Fig2: Mutations of the ADAR1 gene found in patients with dyschromatosis symmetrica hereditaria. a. c.1078C>T (p.R360X) mutation in family 4. b. c.1420C>T (p.R474X) mutation in family 6. c. c.2303G>A (p.W768X) mutation in Sporadic 1. d.c.3248G>A (p.R1083H) mutation in family 7. e.c.3089_3090delGA (p.R1030DfsX1036) mutation in family 1. f. c.2408delG (p.G803VfsX807) mutation in family 3. g. c.3439ins17 (p.D1147VfsX1184) mutation in family 5. h. a nonstop mutation TGA(Stop) CGA(Arg)=Stop1227R in family 2

Mentions: The entire coding and flanking intronic sequences of ADAR1 were screened for mutations among 7 families and 2 sporadic patients of Chinese origin with DSH, we detected six novel ADAR1 mutations and two previously described mutations by direct sequence analysis of the PCR products (Fig. 2). The spectrum of mutations included three nonsense mutations (p.R360X, p.R474X, p.W768X), one missense mutation p.R1083H, three frameshift mutations (p.Arg1030ThrfsX1036, p.Gly803ValfsX807, p.Asp1147ValfsX1184) and one nonstop mutation p.Stop1227R. We failed to detect any ADAR1 mutation in the sporadic 2.Fig. 2


Genetic spectrum of dyschromatosis symmetrica hereditaria in Chinese patients including a novel nonstop mutation in ADAR1 gene.

Zhang G, Shao M, Li Z, Gu Y, Du X, Wang X, Li M - BMC Med. Genet. (2016)

Mutations of the ADAR1 gene found in patients with dyschromatosis symmetrica hereditaria. a. c.1078C>T (p.R360X) mutation in family 4. b. c.1420C>T (p.R474X) mutation in family 6. c. c.2303G>A (p.W768X) mutation in Sporadic 1. d.c.3248G>A (p.R1083H) mutation in family 7. e.c.3089_3090delGA (p.R1030DfsX1036) mutation in family 1. f. c.2408delG (p.G803VfsX807) mutation in family 3. g. c.3439ins17 (p.D1147VfsX1184) mutation in family 5. h. a nonstop mutation TGA(Stop) CGA(Arg)=Stop1227R in family 2
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Related In: Results  -  Collection

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Fig2: Mutations of the ADAR1 gene found in patients with dyschromatosis symmetrica hereditaria. a. c.1078C>T (p.R360X) mutation in family 4. b. c.1420C>T (p.R474X) mutation in family 6. c. c.2303G>A (p.W768X) mutation in Sporadic 1. d.c.3248G>A (p.R1083H) mutation in family 7. e.c.3089_3090delGA (p.R1030DfsX1036) mutation in family 1. f. c.2408delG (p.G803VfsX807) mutation in family 3. g. c.3439ins17 (p.D1147VfsX1184) mutation in family 5. h. a nonstop mutation TGA(Stop) CGA(Arg)=Stop1227R in family 2
Mentions: The entire coding and flanking intronic sequences of ADAR1 were screened for mutations among 7 families and 2 sporadic patients of Chinese origin with DSH, we detected six novel ADAR1 mutations and two previously described mutations by direct sequence analysis of the PCR products (Fig. 2). The spectrum of mutations included three nonsense mutations (p.R360X, p.R474X, p.W768X), one missense mutation p.R1083H, three frameshift mutations (p.Arg1030ThrfsX1036, p.Gly803ValfsX807, p.Asp1147ValfsX1184) and one nonstop mutation p.Stop1227R. We failed to detect any ADAR1 mutation in the sporadic 2.Fig. 2

Bottom Line: In silico analysis proves that all the mutations reported here are pathogenic.This study is useful for functional studies of the protein and to define a diagnostic strategy for mutation screening of the ADAR1 gene.A three-generation family exhibiting phenotypic variability with a single germline ADAR1 mutation suggests that chilblain might aggravate the clinical phenotypes of DSH.

View Article: PubMed Central - PubMed

Affiliation: Department of Phototherapy at Shanghai Skin Disease Hospital & Institute of Photomedicine, Tongji University School of Medicine, 1278, Baode Road, Shanghai, 200443, China. zglamu@163.com.

ABSTRACT

Background: Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant cutaneous disorder caused by the mutations of adenosine deaminase acting on RNA1 (ADAR1) gene. We present a clinical and genetic study of seven unrelated families and two sporadic cases with DSH for mutations in the full coding sequence of ADAR1 gene.

Methods: ADAR1 gene was sequenced in seven unrelated families and two sporadic cases with DSH and 120 controls. Functional significance of the observed ADAR1 mutations was analyzed using PolyPhen 2, SIFT and DDIG-in.

Results: We describe six novel mutations of the ADAR1 gene in Chinese patients with DSH including a nonstop mutation p.Stop1227R, which was firstly reported in ADAR1 gene. In silico analysis proves that all the mutations reported here are pathogenic.

Conclusion: This study is useful for functional studies of the protein and to define a diagnostic strategy for mutation screening of the ADAR1 gene. A three-generation family exhibiting phenotypic variability with a single germline ADAR1 mutation suggests that chilblain might aggravate the clinical phenotypes of DSH.

Show MeSH
Related in: MedlinePlus