Rare hypomagnesemia, seizures, and mental retardation in a 4‐month‐old patient caused by novel CNNM2 mutation Tyr189Cys: Genetic analysis and review
Abstract Background Hypomagnesemia, seizures, and mental retardation (HSMR) syndrome is a rare genetic disease. Presently, only 24 cases have been reported and the clinical features of the disease are yet to be fully described, thereby making diagnosis challenging. Methods Trio‐whole‐exome sequencin...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-04-01
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| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.1898 |
| _version_ | 1819046352298967040 |
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| author | Xiaoyan Xu Shu Hou Weiwei Sun Jing Zhu Jinjing Yuan Zhenzhen Cui De Wu Jiulai Tang |
| author_facet | Xiaoyan Xu Shu Hou Weiwei Sun Jing Zhu Jinjing Yuan Zhenzhen Cui De Wu Jiulai Tang |
| author_sort | Xiaoyan Xu |
| collection | DOAJ |
| description | Abstract Background Hypomagnesemia, seizures, and mental retardation (HSMR) syndrome is a rare genetic disease. Presently, only 24 cases have been reported and the clinical features of the disease are yet to be fully described, thereby making diagnosis challenging. Methods Trio‐whole‐exome sequencing was used for the patient and her parents, and the structure of the variant protein was analyzed by molecular dynamics. Finally, the characteristics of HSMR were summarized by reviewing the previous literature. Results The main disease manifestations in the patient were seizures, liver function damage, hypomagnesemia, atrial septal defect, and sinus arrhythmia. A novel mutation in CNNM2 (c.566A>G/p.Tyr189Cys) was identified by genetic detection. The parents were wild type, and the mutation was rated as pathogenic by American College of Medical Genetics and Genomics guidelines. Ab initio modeling and molecular dynamics simulation show that the mutation destroys the surrounding hydrogen bonds, which may reduce the local stability of the protein structure. In the previous literature, only 24 children with HSMR have been reported, mainly manifested as hypomagnesemia, mental retardation, seizures, and language and motor impairment. Conclusion We have reported the second case of HSMR in the Chinese population, which further expands the phenotypic spectrum of congenital heart disease and the variation spectrum of CNNM2. |
| first_indexed | 2024-12-21T10:43:06Z |
| format | Article |
| id | doaj.art-f67b47c0850f48bc9cb369501bc09fcf |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-12-21T10:43:06Z |
| publishDate | 2022-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-f67b47c0850f48bc9cb369501bc09fcf2022-12-21T19:06:52ZengWileyMolecular Genetics & Genomic Medicine2324-92692022-04-01104n/an/a10.1002/mgg3.1898Rare hypomagnesemia, seizures, and mental retardation in a 4‐month‐old patient caused by novel CNNM2 mutation Tyr189Cys: Genetic analysis and reviewXiaoyan Xu0Shu Hou1Weiwei Sun2Jing Zhu3Jinjing Yuan4Zhenzhen Cui5De Wu6Jiulai Tang7Department of Pediatrics, Neurological Rehabilitation Center the First Affiliated Hospital of Anhui Medical University Hefei ChinaDepartment of Pediatrics the First Affiliated Hospital of Anhui Medical University Hefei ChinaBeijing Chigene Translational Medical Research Center Co. Ltd Beijing ChinaDepartment of Pediatrics, Neurological Rehabilitation Center the First Affiliated Hospital of Anhui Medical University Hefei ChinaDepartment of Pediatrics, Neurological Rehabilitation Center the First Affiliated Hospital of Anhui Medical University Hefei ChinaDepartment of Pediatrics, Neurological Rehabilitation Center the First Affiliated Hospital of Anhui Medical University Hefei ChinaDepartment of Pediatrics, Neurological Rehabilitation Center the First Affiliated Hospital of Anhui Medical University Hefei ChinaDepartment of Pediatrics, Neurological Rehabilitation Center the First Affiliated Hospital of Anhui Medical University Hefei ChinaAbstract Background Hypomagnesemia, seizures, and mental retardation (HSMR) syndrome is a rare genetic disease. Presently, only 24 cases have been reported and the clinical features of the disease are yet to be fully described, thereby making diagnosis challenging. Methods Trio‐whole‐exome sequencing was used for the patient and her parents, and the structure of the variant protein was analyzed by molecular dynamics. Finally, the characteristics of HSMR were summarized by reviewing the previous literature. Results The main disease manifestations in the patient were seizures, liver function damage, hypomagnesemia, atrial septal defect, and sinus arrhythmia. A novel mutation in CNNM2 (c.566A>G/p.Tyr189Cys) was identified by genetic detection. The parents were wild type, and the mutation was rated as pathogenic by American College of Medical Genetics and Genomics guidelines. Ab initio modeling and molecular dynamics simulation show that the mutation destroys the surrounding hydrogen bonds, which may reduce the local stability of the protein structure. In the previous literature, only 24 children with HSMR have been reported, mainly manifested as hypomagnesemia, mental retardation, seizures, and language and motor impairment. Conclusion We have reported the second case of HSMR in the Chinese population, which further expands the phenotypic spectrum of congenital heart disease and the variation spectrum of CNNM2.https://doi.org/10.1002/mgg3.1898CHDCNNM2HSMRhypomagnesemiamental retardationseizures |
| spellingShingle | Xiaoyan Xu Shu Hou Weiwei Sun Jing Zhu Jinjing Yuan Zhenzhen Cui De Wu Jiulai Tang Rare hypomagnesemia, seizures, and mental retardation in a 4‐month‐old patient caused by novel CNNM2 mutation Tyr189Cys: Genetic analysis and review Molecular Genetics & Genomic Medicine CHD CNNM2 HSMR hypomagnesemia mental retardation seizures |
| title | Rare hypomagnesemia, seizures, and mental retardation in a 4‐month‐old patient caused by novel CNNM2 mutation Tyr189Cys: Genetic analysis and review |
| title_full | Rare hypomagnesemia, seizures, and mental retardation in a 4‐month‐old patient caused by novel CNNM2 mutation Tyr189Cys: Genetic analysis and review |
| title_fullStr | Rare hypomagnesemia, seizures, and mental retardation in a 4‐month‐old patient caused by novel CNNM2 mutation Tyr189Cys: Genetic analysis and review |
| title_full_unstemmed | Rare hypomagnesemia, seizures, and mental retardation in a 4‐month‐old patient caused by novel CNNM2 mutation Tyr189Cys: Genetic analysis and review |
| title_short | Rare hypomagnesemia, seizures, and mental retardation in a 4‐month‐old patient caused by novel CNNM2 mutation Tyr189Cys: Genetic analysis and review |
| title_sort | rare hypomagnesemia seizures and mental retardation in a 4 month old patient caused by novel cnnm2 mutation tyr189cys genetic analysis and review |
| topic | CHD CNNM2 HSMR hypomagnesemia mental retardation seizures |
| url | https://doi.org/10.1002/mgg3.1898 |
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