Novel compound heterozygous SUCLG1 variants may contribute to mitochondria DNA depletion syndrome‐9
Abstract Background Succinate‐CoA ligase/synthetase (SCS) deficiency is responsible for encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Variants in SUCLG1, the nuclear gene encoding the alpha subunit of the SCS enzyme playing a pivotal role in maintaining mtDNA in...
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Wiley
2022-09-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.2010 |
| _version_ | 1798000709676826624 |
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| author | Yi‐ming Chen Wei Chen Yue Xu Chao‐sheng Lu Mian‐mian Zhu Rong‐yue Sun Yihong Wang Yuan Chen Jiaming Shi Dan Wang |
| author_facet | Yi‐ming Chen Wei Chen Yue Xu Chao‐sheng Lu Mian‐mian Zhu Rong‐yue Sun Yihong Wang Yuan Chen Jiaming Shi Dan Wang |
| author_sort | Yi‐ming Chen |
| collection | DOAJ |
| description | Abstract Background Succinate‐CoA ligase/synthetase (SCS) deficiency is responsible for encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Variants in SUCLG1, the nuclear gene encoding the alpha subunit of the SCS enzyme playing a pivotal role in maintaining mtDNA integrity and stability, are associated with mitochondrial DNA depletion syndrome 9 (MTDPS9). Methods In this study, we reported an infant with clinical features of MTDPS9 from China. Whole exome sequencing (WES) was used to identify the genetic cause. Bioinformatic analysis and mtDNA level detection were performed to assess pathogenicity. Results The proband manifested with hypotonia, lactic acidosis, mild methylmalonic aciduria, hearing loss and psychomotor retardation. WES identified new compound heterozygous SUCLG1 variants of c.601A>G (p.R201G) in exon 6 and c.871G>C (p.A291P) in exon 8. Computational analysis predicted that these missense variants might alter structure stability and mitochondrial translocation of SUCLG1. qRT‐PCR showed 68% depletion of mtDNA content in proband as compared to controls. Conclusion Novel compound heterozygous variants c.601A>G (p.R201G) and c.871G>C (p.A291P) in SUCLG1 may cause MTDPS9 in this family. Our finding should be helpful for molecular diagnosis, genetic counseling and clinical management of SCS deficiency disorders. |
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| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-11T11:24:44Z |
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| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-5c46ad19e3ca4d9894bc80efdd6216bc2022-12-22T04:26:19ZengWileyMolecular Genetics & Genomic Medicine2324-92692022-09-01109n/an/a10.1002/mgg3.2010Novel compound heterozygous SUCLG1 variants may contribute to mitochondria DNA depletion syndrome‐9Yi‐ming Chen0Wei Chen1Yue Xu2Chao‐sheng Lu3Mian‐mian Zhu4Rong‐yue Sun5Yihong Wang6Yuan Chen7Jiaming Shi8Dan Wang9Department of Surgery The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Wenzhou Zhejiang ChinaDepartment of Radiology The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Wenzhou Zhejiang ChinaDepartment of Pediatrics The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang ChinaDepartment of Pediatrics The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang ChinaDepartment of Pediatrics The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang ChinaDepartment of Pediatrics The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang ChinaDepartment of Pediatrics The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang ChinaDepartment of Pediatrics The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang ChinaDepartment of Pediatrics The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang ChinaDepartment of Pediatrics The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang ChinaAbstract Background Succinate‐CoA ligase/synthetase (SCS) deficiency is responsible for encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Variants in SUCLG1, the nuclear gene encoding the alpha subunit of the SCS enzyme playing a pivotal role in maintaining mtDNA integrity and stability, are associated with mitochondrial DNA depletion syndrome 9 (MTDPS9). Methods In this study, we reported an infant with clinical features of MTDPS9 from China. Whole exome sequencing (WES) was used to identify the genetic cause. Bioinformatic analysis and mtDNA level detection were performed to assess pathogenicity. Results The proband manifested with hypotonia, lactic acidosis, mild methylmalonic aciduria, hearing loss and psychomotor retardation. WES identified new compound heterozygous SUCLG1 variants of c.601A>G (p.R201G) in exon 6 and c.871G>C (p.A291P) in exon 8. Computational analysis predicted that these missense variants might alter structure stability and mitochondrial translocation of SUCLG1. qRT‐PCR showed 68% depletion of mtDNA content in proband as compared to controls. Conclusion Novel compound heterozygous variants c.601A>G (p.R201G) and c.871G>C (p.A291P) in SUCLG1 may cause MTDPS9 in this family. Our finding should be helpful for molecular diagnosis, genetic counseling and clinical management of SCS deficiency disorders.https://doi.org/10.1002/mgg3.2010compound heterozygous variantsmitochondrial DNA depletion syndrome 9mitochondrial encephlomyopathySUCLG1whole exome sequencing |
| spellingShingle | Yi‐ming Chen Wei Chen Yue Xu Chao‐sheng Lu Mian‐mian Zhu Rong‐yue Sun Yihong Wang Yuan Chen Jiaming Shi Dan Wang Novel compound heterozygous SUCLG1 variants may contribute to mitochondria DNA depletion syndrome‐9 Molecular Genetics & Genomic Medicine compound heterozygous variants mitochondrial DNA depletion syndrome 9 mitochondrial encephlomyopathy SUCLG1 whole exome sequencing |
| title | Novel compound heterozygous SUCLG1 variants may contribute to mitochondria DNA depletion syndrome‐9 |
| title_full | Novel compound heterozygous SUCLG1 variants may contribute to mitochondria DNA depletion syndrome‐9 |
| title_fullStr | Novel compound heterozygous SUCLG1 variants may contribute to mitochondria DNA depletion syndrome‐9 |
| title_full_unstemmed | Novel compound heterozygous SUCLG1 variants may contribute to mitochondria DNA depletion syndrome‐9 |
| title_short | Novel compound heterozygous SUCLG1 variants may contribute to mitochondria DNA depletion syndrome‐9 |
| title_sort | novel compound heterozygous suclg1 variants may contribute to mitochondria dna depletion syndrome 9 |
| topic | compound heterozygous variants mitochondrial DNA depletion syndrome 9 mitochondrial encephlomyopathy SUCLG1 whole exome sequencing |
| url | https://doi.org/10.1002/mgg3.2010 |
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