Sökning: onr:"swepub:oai:DiVA.org:umu-194841" >
Infantile SOD1 defi...
Infantile SOD1 deficiency syndrome caused by a homozygous SOD1 variant with absence of enzyme activity
-
- Ezer, Shlomit (författare)
- Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
-
- Daana, Muhannad (författare)
- Child Development Centers, Clalit Health Care Services, Israel
-
- Park, Julien H. (författare)
- Umeå universitet,Neurovetenskaper,Department of General Pediatrics, University of Münster, Münster, Germany
-
visa fler...
-
- Yanovsky-Dagan, Shira (författare)
- Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel
-
- Nordström, Ulrika (författare)
- Umeå universitet,Neurovetenskaper
-
- Basal, Adily (författare)
- Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel
-
- Edvardson, Simon (författare)
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; Pediatric Neurology Unit, Hadassah Medical Organization, Jerusalem, Israel
-
- Saada, Ann (författare)
- Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
-
- Otto, Markus (författare)
- Department of Neurology, University Clinic, Ulm, Germany; Department of Neurology, University Clinic, Halle (Saale), Germany
-
- Meiner, Vardiella (författare)
- Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
-
- Marklund, Stefan L. (författare)
- Umeå universitet,Klinisk kemi
-
- Andersen, Peter Munch, 1962- (författare)
- Umeå universitet,Neurovetenskaper
-
- Harel, Tamar (författare)
- Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
-
visa färre...
-
(creator_code:org_t)
- 2021-11-11
- 2022
- Engelska.
-
Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 145:3, s. 872-878
- Relaterad länk:
-
https://urn.kb.se/re...
-
visa fler...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Pathogenic variants in SOD1, encoding superoxide dismutase 1, are responsible for about 20% of all familial amyotrophic lateral sclerosis cases, through a gain-of-function mechanism. Recently, two reports showed that a specific homozygous SOD1 loss-of-function variant is associated with an infantile progressive motor-neurological syndrome. Exome sequencing followed by molecular studies, including cDNA analysis, SOD1 protein levels and enzymatic activity, and plasma neurofilament light chain levels, were undertaken in an infant with severe global developmental delay, axial hypotonia and limb spasticity. We identified a homozygous 3-bp in-frame deletion in SOD1. cDNA analysis predicted the loss of a single valine residue from a tandem pair (p.Val119/Val120) in the wild-type protein, yet expression levels and splicing were preserved. Analysis of SOD1 activity and protein levels in erythrocyte lysates showed essentially no enzymatic activity and undetectable SOD1 protein in the child, whereas the parents had ∼50% protein expression and activity relative to controls. Neurofilament light chain levels in plasma were elevated, implying ongoing axonal injury and neurodegeneration. Thus, we provide confirmatory evidence of a second biallelic variant in an infant with a severe neurological syndrome and suggest that the in-frame deletion causes instability and subsequent degeneration of SOD1. We highlight the importance of the valine residues at positions V119-120, and suggest possible implications for future therapeutics research.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- amyotrophic lateral sclerosis
- exome sequencing
- SOD1
- superoxide dismutase
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
-
Brain
(Sök värdpublikationen i LIBRIS)
Till lärosätets databas
- Av författaren/redakt...
-
Ezer, Shlomit
-
Daana, Muhannad
-
Park, Julien H.
-
Yanovsky-Dagan, ...
-
Nordström, Ulrik ...
-
Basal, Adily
-
visa fler...
-
Edvardson, Simon
-
Saada, Ann
-
Otto, Markus
-
Meiner, Vardiell ...
-
Marklund, Stefan ...
-
Andersen, Peter ...
-
Harel, Tamar
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Neurologi
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Medicinska och f ...
-
och Neurovetenskaper
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Medicinska och f ...
-
och Medicinsk geneti ...
- Artiklar i publikationen
-
Brain
- Av lärosätet
-
Umeå universitet