Successful Diagnosis of Sengers Syndrome Using a Comprehensive Genomic Analysis
ABSTRACT Background Sengers syndrome is an autosomal recessive mitochondrial DNA depletion syndrome characterized by hypertrophic cardiomyopathy, congenital cataracts, skeletal myopathy, exercise intolerance, and lactic acidosis. Dysfunction of acylglycerol kinase (AGK) is responsible for the diseas...
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Wiley
2025-01-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.70048 |
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| author | Kohta Nakamura Yukiko Yatsuka Sachie Naito Akira Hasegawa Takeya Kasukawa Atsushi Kondo Yoshihito Kishita Yohei Sugiyama Takanori Onuki Tomohiro Ebihara Tomoko Tsuruoka Takuya Fushimi Akira Ohtake Kei Murayama Atsuko Imai‐Okazaki Yasushi Okazaki |
| author_facet | Kohta Nakamura Yukiko Yatsuka Sachie Naito Akira Hasegawa Takeya Kasukawa Atsushi Kondo Yoshihito Kishita Yohei Sugiyama Takanori Onuki Tomohiro Ebihara Tomoko Tsuruoka Takuya Fushimi Akira Ohtake Kei Murayama Atsuko Imai‐Okazaki Yasushi Okazaki |
| author_sort | Kohta Nakamura |
| collection | DOAJ |
| description | ABSTRACT Background Sengers syndrome is an autosomal recessive mitochondrial DNA depletion syndrome characterized by hypertrophic cardiomyopathy, congenital cataracts, skeletal myopathy, exercise intolerance, and lactic acidosis. Dysfunction of acylglycerol kinase (AGK) is responsible for the disease, and several AGK gene variants have been reported. Methods We employed a comprehensive genomic analysis approach, including whole‐genome sequencing and RNA sequencing, combined with various bioinformatics tools. Results Our analysis successfully diagnosed Sengers syndrome in a patient by detecting a known pathogenic variant and a previously unreported large deletion involving the AGK gene in a segmental duplication. Conclusion This study demonstrates the effectiveness of combining multiple genomic analysis approaches for the accurate diagnosis of Sengers syndrome, particularly in cases involving complex genetic variations such as large deletions in segmental duplications. |
| format | Article |
| id | doaj-art-794e5d51c14243d8ac178d74e92b9871 |
| institution | Kabale University |
| issn | 2324-9269 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj-art-794e5d51c14243d8ac178d74e92b98712025-01-24T08:16:42ZengWileyMolecular Genetics & Genomic Medicine2324-92692025-01-01131n/an/a10.1002/mgg3.70048Successful Diagnosis of Sengers Syndrome Using a Comprehensive Genomic AnalysisKohta Nakamura0Yukiko Yatsuka1Sachie Naito2Akira Hasegawa3Takeya Kasukawa4Atsushi Kondo5Yoshihito Kishita6Yohei Sugiyama7Takanori Onuki8Tomohiro Ebihara9Tomoko Tsuruoka10Takuya Fushimi11Akira Ohtake12Kei Murayama13Atsuko Imai‐Okazaki14Yasushi Okazaki15Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine Juntendo University Tokyo JapanDiagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine Juntendo University Tokyo JapanDepartment of Pediatrics Funabashi Central Hospital Chiba JapanLaboratory for Large‐Scale Biomedical Data Technology RIKEN Center for Integrative Medical Sciences Kanagawa JapanLaboratory for Large‐Scale Biomedical Data Technology RIKEN Center for Integrative Medical Sciences Kanagawa JapanLaboratory for Large‐Scale Biomedical Data Technology RIKEN Center for Integrative Medical Sciences Kanagawa JapanDepartment of Life Science, Faculty of Science and Engineering Kindai University Osaka JapanDepartment of Pediatrics, Faculty of Medicine Juntendo University Tokyo JapanDepartment of Metabolism Chiba Children's Hospital Chiba JapanDepartment of Metabolism Chiba Children's Hospital Chiba JapanDepartment of Neonatology Chiba Children's Hospital Chiba JapanDepartment of Metabolism Chiba Children's Hospital Chiba JapanDepartment of Pediatrics & Clinical Genomics Saitama Medical University Saitama JapanDiagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine Juntendo University Tokyo JapanDiagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine Juntendo University Tokyo JapanDiagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine Juntendo University Tokyo JapanABSTRACT Background Sengers syndrome is an autosomal recessive mitochondrial DNA depletion syndrome characterized by hypertrophic cardiomyopathy, congenital cataracts, skeletal myopathy, exercise intolerance, and lactic acidosis. Dysfunction of acylglycerol kinase (AGK) is responsible for the disease, and several AGK gene variants have been reported. Methods We employed a comprehensive genomic analysis approach, including whole‐genome sequencing and RNA sequencing, combined with various bioinformatics tools. Results Our analysis successfully diagnosed Sengers syndrome in a patient by detecting a known pathogenic variant and a previously unreported large deletion involving the AGK gene in a segmental duplication. Conclusion This study demonstrates the effectiveness of combining multiple genomic analysis approaches for the accurate diagnosis of Sengers syndrome, particularly in cases involving complex genetic variations such as large deletions in segmental duplications.https://doi.org/10.1002/mgg3.70048genetic analysismitochondrial diseasemitochondrial DNA depletion syndromemitochondrial respiratory chain complex deficienciesSengers syndrome |
| spellingShingle | Kohta Nakamura Yukiko Yatsuka Sachie Naito Akira Hasegawa Takeya Kasukawa Atsushi Kondo Yoshihito Kishita Yohei Sugiyama Takanori Onuki Tomohiro Ebihara Tomoko Tsuruoka Takuya Fushimi Akira Ohtake Kei Murayama Atsuko Imai‐Okazaki Yasushi Okazaki Successful Diagnosis of Sengers Syndrome Using a Comprehensive Genomic Analysis Molecular Genetics & Genomic Medicine genetic analysis mitochondrial disease mitochondrial DNA depletion syndrome mitochondrial respiratory chain complex deficiencies Sengers syndrome |
| title | Successful Diagnosis of Sengers Syndrome Using a Comprehensive Genomic Analysis |
| title_full | Successful Diagnosis of Sengers Syndrome Using a Comprehensive Genomic Analysis |
| title_fullStr | Successful Diagnosis of Sengers Syndrome Using a Comprehensive Genomic Analysis |
| title_full_unstemmed | Successful Diagnosis of Sengers Syndrome Using a Comprehensive Genomic Analysis |
| title_short | Successful Diagnosis of Sengers Syndrome Using a Comprehensive Genomic Analysis |
| title_sort | successful diagnosis of sengers syndrome using a comprehensive genomic analysis |
| topic | genetic analysis mitochondrial disease mitochondrial DNA depletion syndrome mitochondrial respiratory chain complex deficiencies Sengers syndrome |
| url | https://doi.org/10.1002/mgg3.70048 |
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