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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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Related in: MedlinePlus

Clinical presentation of dyschromatosis symmetrica hereditaria (DSH) patients. a.. Freckle-like pigmented macules on the face (proband of family 3, severe phenotype). b. Freckle-like pigmented macules on the face of the proband in family 7. c. No freckle-like macules on the face of the patient II:3 in family 7. d. Dense freckle-like macules on the neck and face (proband of family 2, severe phenotype). e. Freckle-like pigmented macules on the face of the sporadic 2. f. Hypopigmented and hyperpigmented macules on the dorsal aspects of the extremities of hands and feet (proband of family 3, severe phenotype). g. Hypopigmented and hyperpigmented macules on the dorsal aspects of hands of the proband in family 7 (mild phenotype). h. No any lesion on the dorsal aspect of hand of the patient II:2 in family 7. i, j. Hypopigmented and hyperpigmented macules on the dorsal aspect of the hand (the patient II:3 in family 7 and the proband in family 2 , severe phenotype). k. Hypopigmented and hyperpigmented macules on the dorsal aspect of the hand of the sporadic 2. l. Few small freckle-like pigmented macules disturbed on the back of the foot (the patient II:2 in family 7). m, n. Hypopigmented and hyperpigmented macules on the back of the foot (the patient II:3 in family 7 and the proband in family 2, severe phenotype). o. Few small freckle-like pigmented macules disturbed on the back of the foot (the sporadic 2, mild phenotype)
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Fig1: Clinical presentation of dyschromatosis symmetrica hereditaria (DSH) patients. a.. Freckle-like pigmented macules on the face (proband of family 3, severe phenotype). b. Freckle-like pigmented macules on the face of the proband in family 7. c. No freckle-like macules on the face of the patient II:3 in family 7. d. Dense freckle-like macules on the neck and face (proband of family 2, severe phenotype). e. Freckle-like pigmented macules on the face of the sporadic 2. f. Hypopigmented and hyperpigmented macules on the dorsal aspects of the extremities of hands and feet (proband of family 3, severe phenotype). g. Hypopigmented and hyperpigmented macules on the dorsal aspects of hands of the proband in family 7 (mild phenotype). h. No any lesion on the dorsal aspect of hand of the patient II:2 in family 7. i, j. Hypopigmented and hyperpigmented macules on the dorsal aspect of the hand (the patient II:3 in family 7 and the proband in family 2 , severe phenotype). k. Hypopigmented and hyperpigmented macules on the dorsal aspect of the hand of the sporadic 2. l. Few small freckle-like pigmented macules disturbed on the back of the foot (the patient II:2 in family 7). m, n. Hypopigmented and hyperpigmented macules on the back of the foot (the patient II:3 in family 7 and the proband in family 2, severe phenotype). o. Few small freckle-like pigmented macules disturbed on the back of the foot (the sporadic 2, mild phenotype)

Mentions: This study investigated 7 families (Family 1–7) and 2 sporadic cases with DSH in the Chinese population. DSH was diagnosed by experienced dermatologists based on the typical manifestations and histopathological findings. Seven multi-generation DSH families exhibited autosomal dominant inheritance. All affected individuals had a typical mixture of hyperpigmented and hypopigmented macules on the extremities (Fig. 1a, 1f). These lesions were of irregular shapes and sizes, which appears during early childhood, generally ranging from 3 to 15 years. Table 1 summarizes the clinical findings of all the patients analyzed in this study. Noteworthy is that a variable clinical phenotype was observed in family 7. The proband in family 7 was a 23-year-old female. She presented with asymptomatic hyperpigmented and hypopigmented macules on her extremities and had been developing freckle-like macules on her face since she was 7 years old  (Figure 1b, g). Her mother has only a few small freckle-like pigmented macules disturbed on the back of her feet  (Figure 1h, l). Whereas her uncle (II:3) had many more asymptomatic hyperpigmented and hypopigmented macules on his extremities than the proband but no freckle-like macules on his face (Figure 1c, i, m). There is no systematic involvement was noticed in any of our patients.Fig. 1


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)

Clinical presentation of dyschromatosis symmetrica hereditaria (DSH) patients. a.. Freckle-like pigmented macules on the face (proband of family 3, severe phenotype). b. Freckle-like pigmented macules on the face of the proband in family 7. c. No freckle-like macules on the face of the patient II:3 in family 7. d. Dense freckle-like macules on the neck and face (proband of family 2, severe phenotype). e. Freckle-like pigmented macules on the face of the sporadic 2. f. Hypopigmented and hyperpigmented macules on the dorsal aspects of the extremities of hands and feet (proband of family 3, severe phenotype). g. Hypopigmented and hyperpigmented macules on the dorsal aspects of hands of the proband in family 7 (mild phenotype). h. No any lesion on the dorsal aspect of hand of the patient II:2 in family 7. i, j. Hypopigmented and hyperpigmented macules on the dorsal aspect of the hand (the patient II:3 in family 7 and the proband in family 2 , severe phenotype). k. Hypopigmented and hyperpigmented macules on the dorsal aspect of the hand of the sporadic 2. l. Few small freckle-like pigmented macules disturbed on the back of the foot (the patient II:2 in family 7). m, n. Hypopigmented and hyperpigmented macules on the back of the foot (the patient II:3 in family 7 and the proband in family 2, severe phenotype). o. Few small freckle-like pigmented macules disturbed on the back of the foot (the sporadic 2, mild phenotype)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4759768&req=5

Fig1: Clinical presentation of dyschromatosis symmetrica hereditaria (DSH) patients. a.. Freckle-like pigmented macules on the face (proband of family 3, severe phenotype). b. Freckle-like pigmented macules on the face of the proband in family 7. c. No freckle-like macules on the face of the patient II:3 in family 7. d. Dense freckle-like macules on the neck and face (proband of family 2, severe phenotype). e. Freckle-like pigmented macules on the face of the sporadic 2. f. Hypopigmented and hyperpigmented macules on the dorsal aspects of the extremities of hands and feet (proband of family 3, severe phenotype). g. Hypopigmented and hyperpigmented macules on the dorsal aspects of hands of the proband in family 7 (mild phenotype). h. No any lesion on the dorsal aspect of hand of the patient II:2 in family 7. i, j. Hypopigmented and hyperpigmented macules on the dorsal aspect of the hand (the patient II:3 in family 7 and the proband in family 2 , severe phenotype). k. Hypopigmented and hyperpigmented macules on the dorsal aspect of the hand of the sporadic 2. l. Few small freckle-like pigmented macules disturbed on the back of the foot (the patient II:2 in family 7). m, n. Hypopigmented and hyperpigmented macules on the back of the foot (the patient II:3 in family 7 and the proband in family 2, severe phenotype). o. Few small freckle-like pigmented macules disturbed on the back of the foot (the sporadic 2, mild phenotype)
Mentions: This study investigated 7 families (Family 1–7) and 2 sporadic cases with DSH in the Chinese population. DSH was diagnosed by experienced dermatologists based on the typical manifestations and histopathological findings. Seven multi-generation DSH families exhibited autosomal dominant inheritance. All affected individuals had a typical mixture of hyperpigmented and hypopigmented macules on the extremities (Fig. 1a, 1f). These lesions were of irregular shapes and sizes, which appears during early childhood, generally ranging from 3 to 15 years. Table 1 summarizes the clinical findings of all the patients analyzed in this study. Noteworthy is that a variable clinical phenotype was observed in family 7. The proband in family 7 was a 23-year-old female. She presented with asymptomatic hyperpigmented and hypopigmented macules on her extremities and had been developing freckle-like macules on her face since she was 7 years old  (Figure 1b, g). Her mother has only a few small freckle-like pigmented macules disturbed on the back of her feet  (Figure 1h, l). Whereas her uncle (II:3) had many more asymptomatic hyperpigmented and hypopigmented macules on his extremities than the proband but no freckle-like macules on his face (Figure 1c, i, m). There is no systematic involvement was noticed in any of our patients.Fig. 1

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