Identification of a novel SUOX pathogenic variants as the cause of isolated sulfite oxidase deficiency in a Chinese pedigree
Abstract Background Isolated sulfite oxidase deficiency (ISOD) is a life‐threatening rare autosomal recessive disorder caused by pathogenic variants in SUOX (OMIM 606887) gene. The aim of our study was to establish a comprehensive genetic diagnosis strategy for the pathogenicity analysis of the SUOX...
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| Format: | Article |
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Wiley
2021-02-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.1590 |
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| author | Peng Du Reem N. Hassan Hualei Luo Jie Xie Yue Zhu Qiuyue Hu Jin Yan Weiying Jiang |
| author_facet | Peng Du Reem N. Hassan Hualei Luo Jie Xie Yue Zhu Qiuyue Hu Jin Yan Weiying Jiang |
| author_sort | Peng Du |
| collection | DOAJ |
| description | Abstract Background Isolated sulfite oxidase deficiency (ISOD) is a life‐threatening rare autosomal recessive disorder caused by pathogenic variants in SUOX (OMIM 606887) gene. The aim of our study was to establish a comprehensive genetic diagnosis strategy for the pathogenicity analysis of the SUOX gene within a limited time and to lay the foundation for precise genetic counseling, prenatal diagnosis, and preimplantation genetic diagnosis. Methods Two offspring from one set of parents were studied. Next‐generation sequencing (NGS) was used to screen for disease‐causing gene variants in a family with ISOD. Then, Sanger sequencing was performed to verify the presence of candidate variants. Sulfite, homocysteine and uric acid levels were detected in the patients. According to the ACMG/AMP guidelines, the pathogenicity level of novel variants was annotated. Results The nonsense pathogenic variant (c.1200C > G (p.Y400*)) and a duplication (c.1549_1574dup (p.I525 Mfs*102)) were found in the SUOX gene in the proband. The nonsense mutation (c.1200C > G (p.Y400*), pathogenic, isolated sulfite oxidase deficiency, autosomal recessive) has been reported as pathogenic and the duplication (c.1549_1574dup (p.I525 Mfs*102), pathogenic, isolated sulfite oxidase deficiency, autosomal recessive) was novel, which was classified as pathogenic according to the ACMG/AMP Standards and Guidelines. Conclusion We established the pathogenicity assessment in ISOD patients based on ACMG/AMP Standards and Guidelines and this is the first ISOD patient reported in mainland China. We also discovered that ISOD is caused by SUOX gene duplication mutation, which enriches the spectrum of SUOX pathogenic variants. |
| first_indexed | 2024-03-07T23:15:47Z |
| format | Article |
| id | doaj.art-33acfdf6853c40c0b80e0ef71569408e |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:15:47Z |
| publishDate | 2021-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-33acfdf6853c40c0b80e0ef71569408e2024-02-21T11:37:44ZengWileyMolecular Genetics & Genomic Medicine2324-92692021-02-0192n/an/a10.1002/mgg3.1590Identification of a novel SUOX pathogenic variants as the cause of isolated sulfite oxidase deficiency in a Chinese pedigreePeng Du0Reem N. Hassan1Hualei Luo2Jie Xie3Yue Zhu4Qiuyue Hu5Jin Yan6Weiying Jiang7Department of Medical Genetics ZhongShan School of MedicineSun Yat‐sen University Guangzhou ChinaDepartment of Medical Genetics ZhongShan School of MedicineSun Yat‐sen University Guangzhou ChinaDepartment of Medical Genetics ZhongShan School of MedicineSun Yat‐sen University Guangzhou ChinaDepartment of Medical Genetics ZhongShan School of MedicineSun Yat‐sen University Guangzhou ChinaDepartment of Medical Genetics ZhongShan School of MedicineSun Yat‐sen University Guangzhou ChinaDepartment of Medical Genetics ZhongShan School of MedicineSun Yat‐sen University Guangzhou ChinaDepartment of Medical Genetics ZhongShan School of MedicineSun Yat‐sen University Guangzhou ChinaDepartment of Medical Genetics ZhongShan School of MedicineSun Yat‐sen University Guangzhou ChinaAbstract Background Isolated sulfite oxidase deficiency (ISOD) is a life‐threatening rare autosomal recessive disorder caused by pathogenic variants in SUOX (OMIM 606887) gene. The aim of our study was to establish a comprehensive genetic diagnosis strategy for the pathogenicity analysis of the SUOX gene within a limited time and to lay the foundation for precise genetic counseling, prenatal diagnosis, and preimplantation genetic diagnosis. Methods Two offspring from one set of parents were studied. Next‐generation sequencing (NGS) was used to screen for disease‐causing gene variants in a family with ISOD. Then, Sanger sequencing was performed to verify the presence of candidate variants. Sulfite, homocysteine and uric acid levels were detected in the patients. According to the ACMG/AMP guidelines, the pathogenicity level of novel variants was annotated. Results The nonsense pathogenic variant (c.1200C > G (p.Y400*)) and a duplication (c.1549_1574dup (p.I525 Mfs*102)) were found in the SUOX gene in the proband. The nonsense mutation (c.1200C > G (p.Y400*), pathogenic, isolated sulfite oxidase deficiency, autosomal recessive) has been reported as pathogenic and the duplication (c.1549_1574dup (p.I525 Mfs*102), pathogenic, isolated sulfite oxidase deficiency, autosomal recessive) was novel, which was classified as pathogenic according to the ACMG/AMP Standards and Guidelines. Conclusion We established the pathogenicity assessment in ISOD patients based on ACMG/AMP Standards and Guidelines and this is the first ISOD patient reported in mainland China. We also discovered that ISOD is caused by SUOX gene duplication mutation, which enriches the spectrum of SUOX pathogenic variants.https://doi.org/10.1002/mgg3.1590homocysteineisolated sulfite oxidase deficiencynovel mutationpathogenic identificationsulfite oxidaseSUOX |
| spellingShingle | Peng Du Reem N. Hassan Hualei Luo Jie Xie Yue Zhu Qiuyue Hu Jin Yan Weiying Jiang Identification of a novel SUOX pathogenic variants as the cause of isolated sulfite oxidase deficiency in a Chinese pedigree Molecular Genetics & Genomic Medicine homocysteine isolated sulfite oxidase deficiency novel mutation pathogenic identification sulfite oxidase SUOX |
| title | Identification of a novel SUOX pathogenic variants as the cause of isolated sulfite oxidase deficiency in a Chinese pedigree |
| title_full | Identification of a novel SUOX pathogenic variants as the cause of isolated sulfite oxidase deficiency in a Chinese pedigree |
| title_fullStr | Identification of a novel SUOX pathogenic variants as the cause of isolated sulfite oxidase deficiency in a Chinese pedigree |
| title_full_unstemmed | Identification of a novel SUOX pathogenic variants as the cause of isolated sulfite oxidase deficiency in a Chinese pedigree |
| title_short | Identification of a novel SUOX pathogenic variants as the cause of isolated sulfite oxidase deficiency in a Chinese pedigree |
| title_sort | identification of a novel suox pathogenic variants as the cause of isolated sulfite oxidase deficiency in a chinese pedigree |
| topic | homocysteine isolated sulfite oxidase deficiency novel mutation pathogenic identification sulfite oxidase SUOX |
| url | https://doi.org/10.1002/mgg3.1590 |
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