Severe Form of ßIV-Spectrin Deficiency With Mitochondrial Dysfunction and Cardiomyopathy—A Case Report
ßIV-spectrin is a protein of the spectrin family which is involved in the organization of the cytoskeleton structure and is found in high quantity in the axon initial segment and the nodes of Ranvier. Together with ankyrin G, ßIV-spectrin is responsible for the clustering of KCNQ2/3-potassium channe...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2021.643805/full |
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| author | Aziza Miriam Belkheir Janine Reunert Christiane Elpers Lambert van den Heuvel Richard Rodenburg Anja Seelhöfer Stephan Rust Astrid Jeibmann Michael Frosch Thorsten Marquardt |
| author_facet | Aziza Miriam Belkheir Janine Reunert Christiane Elpers Lambert van den Heuvel Richard Rodenburg Anja Seelhöfer Stephan Rust Astrid Jeibmann Michael Frosch Thorsten Marquardt |
| author_sort | Aziza Miriam Belkheir |
| collection | DOAJ |
| description | ßIV-spectrin is a protein of the spectrin family which is involved in the organization of the cytoskeleton structure and is found in high quantity in the axon initial segment and the nodes of Ranvier. Together with ankyrin G, ßIV-spectrin is responsible for the clustering of KCNQ2/3-potassium channels and NaV-sodium channels. Loss or reduction of ßIV-spectrin causes a destabilization of the cytoskeleton and an impairment in the generation of the action potential, which leads to neuronal degeneration. Furthermore, ßIV-spectrin has been described to play an important role in the maintenance of the neuronal polarity and of the diffusion barrier. ßIV-spectrin is also located in the heart where it takes an important part in the structural organization of ion channels and has also been described to participate in cell signaling pathways through binding of transcription factors. We describe two patients with a severe form of ßIV-spectrin deficiency. Whole-exome sequencing revealed the homozygous stop mutation c.6016C>T (p.R2006*) in the SPTBN4 gene. The phenotype of these patients is characterized by profound psychomotor developmental arrest, respiratory insufficiency and deafness. Additionally one of the patients presents with cardiomyopathy, optical nerve atrophy, and mitochondrial dysfunction. This is the first report of a severe form of ßIV-spectrin deficiency with hypertrophic cardiomyopathy and mitochondrial dysfunction. |
| first_indexed | 2024-12-14T03:57:55Z |
| format | Article |
| id | doaj.art-5ea2c2d167bc4ff88f141e7678fb8989 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-14T03:57:55Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-5ea2c2d167bc4ff88f141e7678fb89892022-12-21T23:18:02ZengFrontiers Media S.A.Frontiers in Neurology1664-22952021-04-011210.3389/fneur.2021.643805643805Severe Form of ßIV-Spectrin Deficiency With Mitochondrial Dysfunction and Cardiomyopathy—A Case ReportAziza Miriam Belkheir0Janine Reunert1Christiane Elpers2Lambert van den Heuvel3Richard Rodenburg4Anja Seelhöfer5Stephan Rust6Astrid Jeibmann7Michael Frosch8Thorsten Marquardt9Department of General Paediatrics, Metabolic Diseases, University Children's Hospital Muenster, Münster, GermanyDepartment of General Paediatrics, Metabolic Diseases, University Children's Hospital Muenster, Münster, GermanyDepartment of General Paediatrics, Metabolic Diseases, University Children's Hospital Muenster, Münster, GermanyTranslational Metabolic Laboratory, Department of Paediatrics, Radboud Center for Mitochondrial Medicine, Radboud UMC, Nijmegen, NetherlandsTranslational Metabolic Laboratory, Department of Paediatrics, Radboud Center for Mitochondrial Medicine, Radboud UMC, Nijmegen, NetherlandsDepartment of General Paediatrics, Metabolic Diseases, University Children's Hospital Muenster, Münster, GermanyDepartment of General Paediatrics, Metabolic Diseases, University Children's Hospital Muenster, Münster, GermanyInstitute of Neuropathology, University Hospital Muenster, Münster, GermanyDepartment of Children's Pain Therapy and Paediatric Palliative Care, Faculty of Health—School of Medicine, Witten/Herdecke University, Witten, GermanyDepartment of General Paediatrics, Metabolic Diseases, University Children's Hospital Muenster, Münster, GermanyßIV-spectrin is a protein of the spectrin family which is involved in the organization of the cytoskeleton structure and is found in high quantity in the axon initial segment and the nodes of Ranvier. Together with ankyrin G, ßIV-spectrin is responsible for the clustering of KCNQ2/3-potassium channels and NaV-sodium channels. Loss or reduction of ßIV-spectrin causes a destabilization of the cytoskeleton and an impairment in the generation of the action potential, which leads to neuronal degeneration. Furthermore, ßIV-spectrin has been described to play an important role in the maintenance of the neuronal polarity and of the diffusion barrier. ßIV-spectrin is also located in the heart where it takes an important part in the structural organization of ion channels and has also been described to participate in cell signaling pathways through binding of transcription factors. We describe two patients with a severe form of ßIV-spectrin deficiency. Whole-exome sequencing revealed the homozygous stop mutation c.6016C>T (p.R2006*) in the SPTBN4 gene. The phenotype of these patients is characterized by profound psychomotor developmental arrest, respiratory insufficiency and deafness. Additionally one of the patients presents with cardiomyopathy, optical nerve atrophy, and mitochondrial dysfunction. This is the first report of a severe form of ßIV-spectrin deficiency with hypertrophic cardiomyopathy and mitochondrial dysfunction.https://www.frontiersin.org/articles/10.3389/fneur.2021.643805/fullßIV-spectrin deficiencymitochondrial dysfunctionneurodegenerationcardiomyopathypsychomotor developmental arrestcase report |
| spellingShingle | Aziza Miriam Belkheir Janine Reunert Christiane Elpers Lambert van den Heuvel Richard Rodenburg Anja Seelhöfer Stephan Rust Astrid Jeibmann Michael Frosch Thorsten Marquardt Severe Form of ßIV-Spectrin Deficiency With Mitochondrial Dysfunction and Cardiomyopathy—A Case Report Frontiers in Neurology ßIV-spectrin deficiency mitochondrial dysfunction neurodegeneration cardiomyopathy psychomotor developmental arrest case report |
| title | Severe Form of ßIV-Spectrin Deficiency With Mitochondrial Dysfunction and Cardiomyopathy—A Case Report |
| title_full | Severe Form of ßIV-Spectrin Deficiency With Mitochondrial Dysfunction and Cardiomyopathy—A Case Report |
| title_fullStr | Severe Form of ßIV-Spectrin Deficiency With Mitochondrial Dysfunction and Cardiomyopathy—A Case Report |
| title_full_unstemmed | Severe Form of ßIV-Spectrin Deficiency With Mitochondrial Dysfunction and Cardiomyopathy—A Case Report |
| title_short | Severe Form of ßIV-Spectrin Deficiency With Mitochondrial Dysfunction and Cardiomyopathy—A Case Report |
| title_sort | severe form of ssiv spectrin deficiency with mitochondrial dysfunction and cardiomyopathy a case report |
| topic | ßIV-spectrin deficiency mitochondrial dysfunction neurodegeneration cardiomyopathy psychomotor developmental arrest case report |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2021.643805/full |
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