Identification of five novel variants of ADAR1 in dyschromatosis symmetrica hereditaria by next-generation sequencing
BackgroundDyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant inherited pigmentary dermatosis characterized by a mixture of hyperpigmented and hypopigmented freckles on the dorsal aspect of the distal extremities. To date, pathogenic mutations causing DSH have been identified in...
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2023.1161502/full |
| _version_ | 1797786664968388608 |
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| author | Qian Ma Lingyi Che Yibing Chen Zhuoyu Gu |
| author_facet | Qian Ma Lingyi Che Yibing Chen Zhuoyu Gu |
| author_sort | Qian Ma |
| collection | DOAJ |
| description | BackgroundDyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant inherited pigmentary dermatosis characterized by a mixture of hyperpigmented and hypopigmented freckles on the dorsal aspect of the distal extremities. To date, pathogenic mutations causing DSH have been identified in the adenosine deaminase acting on RNA1 gene (ADAR1), which is mapped to chromosome 1q21.ObjectiveThe present study aimed to investigate the underlying pathological mechanism in 14 patients with DSH from five unrelated Chinese families. Next-generation sequencing (NGS) and direct sequencing were performed on a proband with DSH to identify causative mutations. All coding, adjacent intronic, and 5′- and 3′-untranslated regions of ADAR1 were screened, and variants were identified.ResultThese mutations consisted of three missense mutations (NM_001025107: c.716G>A, NM_001111.5: c.3384G>C, and NM_001111.5: c.3385T>G), one nonsense mutation (NM_001111.5:c.511G>T), and one splice-site mutation (NM_001111.5: c.2080-1G>T) located in exon 2, exon 14, and the adjacent intronic region according to recommended Human Genome Variation Society (HGVS) nomenclature. Moreover, using polymerase chain reaction and Sanger sequencing, we identified five novel ADAR1 variants, which can be predicted to be pathogenic by in silico genome sequence analysis. Among the mutations, the missense mutations had no significant effect on the spatial structure of the protein, while the stop codon introduced by the nonsense mutation truncated the protein.ConclusionOur results highlighted that the advent of NGS has facilitated high-throughput screening for the identification of disease-causing mutations with high accuracy, stability, and specificity. Five novel genetic mutations were found in five unrelated families, thereby extending the pathogenic mutational spectrum of ADAR1 in DSH and providing new insights into this complex genetic disorder. |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-13T01:12:06Z |
| publishDate | 2023-07-01 |
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| series | Frontiers in Pediatrics |
| spelling | doaj.art-cc464ad33c2e430492b17804ff2f52062023-07-05T20:29:54ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602023-07-011110.3389/fped.2023.11615021161502Identification of five novel variants of ADAR1 in dyschromatosis symmetrica hereditaria by next-generation sequencingQian Ma0Lingyi Che1Yibing Chen2Zhuoyu Gu3Genetic and Prenatal Diagnosis Center, Department of Gynecology and Obstetrics, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, ChinaGenetic and Prenatal Diagnosis Center, Department of Gynecology and Obstetrics, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, ChinaGenetic and Prenatal Diagnosis Center, Department of Gynecology and Obstetrics, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, ChinaBackgroundDyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant inherited pigmentary dermatosis characterized by a mixture of hyperpigmented and hypopigmented freckles on the dorsal aspect of the distal extremities. To date, pathogenic mutations causing DSH have been identified in the adenosine deaminase acting on RNA1 gene (ADAR1), which is mapped to chromosome 1q21.ObjectiveThe present study aimed to investigate the underlying pathological mechanism in 14 patients with DSH from five unrelated Chinese families. Next-generation sequencing (NGS) and direct sequencing were performed on a proband with DSH to identify causative mutations. All coding, adjacent intronic, and 5′- and 3′-untranslated regions of ADAR1 were screened, and variants were identified.ResultThese mutations consisted of three missense mutations (NM_001025107: c.716G>A, NM_001111.5: c.3384G>C, and NM_001111.5: c.3385T>G), one nonsense mutation (NM_001111.5:c.511G>T), and one splice-site mutation (NM_001111.5: c.2080-1G>T) located in exon 2, exon 14, and the adjacent intronic region according to recommended Human Genome Variation Society (HGVS) nomenclature. Moreover, using polymerase chain reaction and Sanger sequencing, we identified five novel ADAR1 variants, which can be predicted to be pathogenic by in silico genome sequence analysis. Among the mutations, the missense mutations had no significant effect on the spatial structure of the protein, while the stop codon introduced by the nonsense mutation truncated the protein.ConclusionOur results highlighted that the advent of NGS has facilitated high-throughput screening for the identification of disease-causing mutations with high accuracy, stability, and specificity. Five novel genetic mutations were found in five unrelated families, thereby extending the pathogenic mutational spectrum of ADAR1 in DSH and providing new insights into this complex genetic disorder.https://www.frontiersin.org/articles/10.3389/fped.2023.1161502/fullnext-generation sequencingdyschromatosis ymmetrica hereditariaADAR1mutationshyperpigmented and hypopigmented |
| spellingShingle | Qian Ma Lingyi Che Yibing Chen Zhuoyu Gu Identification of five novel variants of ADAR1 in dyschromatosis symmetrica hereditaria by next-generation sequencing Frontiers in Pediatrics next-generation sequencing dyschromatosis ymmetrica hereditaria ADAR1 mutations hyperpigmented and hypopigmented |
| title | Identification of five novel variants of ADAR1 in dyschromatosis symmetrica hereditaria by next-generation sequencing |
| title_full | Identification of five novel variants of ADAR1 in dyschromatosis symmetrica hereditaria by next-generation sequencing |
| title_fullStr | Identification of five novel variants of ADAR1 in dyschromatosis symmetrica hereditaria by next-generation sequencing |
| title_full_unstemmed | Identification of five novel variants of ADAR1 in dyschromatosis symmetrica hereditaria by next-generation sequencing |
| title_short | Identification of five novel variants of ADAR1 in dyschromatosis symmetrica hereditaria by next-generation sequencing |
| title_sort | identification of five novel variants of adar1 in dyschromatosis symmetrica hereditaria by next generation sequencing |
| topic | next-generation sequencing dyschromatosis ymmetrica hereditaria ADAR1 mutations hyperpigmented and hypopigmented |
| url | https://www.frontiersin.org/articles/10.3389/fped.2023.1161502/full |
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