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A novel homozygous ...
A novel homozygous p.Ser69Pro SOD1 mutation causes severe young-onset ALS with decreased enzyme activity
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- Fahmy, Nagia (författare)
- Neuromuscular Unit, Faculty of Medicine, Ain Shams University, Cairo, Egypt; Neuromuscular Research Unit, Neuropsychiatry Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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- Müller, Kathrin (författare)
- Department of Neurology, Ulm University, Ulm, Germany; Institute of Human Genetics, Ulm University, Ulm University Medical Center, Ulm, Germany
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- Andersen, Peter Munch, 1962- (författare)
- Umeå universitet,Neurovetenskaper
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- Marklund, Stefan L. (författare)
- Umeå universitet,Klinisk kemi
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- Otto, Markus (författare)
- Department of Neurology, Ulm University, Ulm, Germany
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- Ludolph, Albert C. (författare)
- Department of Neurology, Ulm University, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm Site, Ulm, Germany
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- Hamdi, Nabila (författare)
- Molecular Pathology Unit, The German University in Cairo, Cairo, Egypt
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(creator_code:org_t)
- 2022-12-06
- 2023
- Engelska.
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Ingår i: Journal of Neurology. - : Springer. - 0340-5354 .- 1432-1459. ; 270, s. 1770-1773
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: The dose–effect of various SOD1 mutations on SOD1 enzymatic activity offers valuable insights into ALS pathogenesis with possible therapeutic implications. Homozygous SOD1 mutations, yet scarce, are of special interest. We report a novel homozygous SOD1 mutation with decreased enzymatic activity and severe early onset ALS phenotype.Methods: Whole exome sequencing and targeted screening of commonly implicated genes were conducted. Repeat-primed PCR and fragment length analysis were used for C9orf72. Bi-directional Sanger sequencing was used for SOD1 and other genes. SOD1 activity was measured by direct spectrophotometry. Serum neurofilament light chain level was measured by the ELLA immunoassay system.Results: The homozygous patient for a novel SOD1 variant p.Ser69Pro showed poor SOD1 enzymatic activity (16% of controls) and an early onset ALS phenotype predominantly affecting lower motor neurons with rapid involvement of the trunk, upper limbs and bulbar muscles. The asymptomatic heterozygous relatives had at least 68% of normal enzyme activity. Level of serum neurofilament light chain was much higher (148 pg/ml) in the patient than the relatives who had normal levels (6–10 pg/ml).Conclusion: This novel mutation adds knowledge to the ALS genotype–phenotype spectrum and supports the strong dose–effect of SOD1 mutations associated with severely decreased enzymatic activity.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Nyckelord
- Enzyme activity
- Homozygous
- Novel mutation
- SOD1
- Young-onset
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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