Search: onr:"swepub:oai:DiVA.org:umu-189488" >
De novo mutations i...
De novo mutations in SOD1 are a cause of ALS
-
Müller, Kathrin (author)
-
Oh, Ki-Wook (author)
-
- Nordin, Angelica (author)
- Umeå universitet,Neurovetenskaper
-
show more...
-
Panthi, Sudhan (author)
-
Kim, Seung Hyun (author)
-
- Nordin, Frida (author)
- Umeå universitet,Neurovetenskaper
-
Freischmidt, Axel (author)
-
Ludolph, Albert C. (author)
-
Ki, Chang Seok (author)
-
- Forsberg, Karin (author)
- Umeå universitet,Neurovetenskaper,Patologi
-
Weishaupt, Jochen (author)
-
Kim, Young-Eun (author)
-
- Andersen, Peter Munch, 1962- (author)
- Umeå universitet,Neurovetenskaper
-
show less...
-
(creator_code:org_t)
- 2021-09-13
- 2022
- English.
-
In: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 93, s. 201-206
- Related links:
-
https://doi.org/10.1...
-
show more...
-
https://umu.diva-por... (primary) (Raw object)
-
https://jnnp.bmj.com...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- Objective: The only identified cause of amyotrophic lateral sclerosis (ALS) are mutations in a number of genes found in familial cases but also in sporadic cases. De novo mutations occurring in a parental gonadal cell, in the zygote or postzygotic during embryonal development can result in an apparently sporadic/isolated case of ALS later in life. We searched for de novo mutations in SOD1 as a cause of ALS.Methods: We analysed peripheral-blood exome, genome and Sanger sequencing to identify deleterious mutations in SOD1 in 4000 ALS patients from Germany, South Korea and Sweden. Parental kinship was confirmed using highly polymorphic microsatellite markers across the genome. Medical genealogical and clinical data were reviewed and compared with the literature.Results: We identified four sporadic ALS cases with de novo mutations in SOD1. They aggregate in hot-spot codons earlier found mutated in familial cases. Their phenotypes match closely what has earlier been reported in familial cases with pathogenic mutations in SOD1. We also encountered familial cases where de novo mutational events in recent generations may have been involved.Conclusions: De novo mutations are a cause of sporadic ALS and may also be underpinning smaller families with few affected ALS cases. It was not possible to ascertain if the origin of the de novo mutations was parental germline, zygotic or postzygotic during embryonal development. All ALS patients should be offered genetic counselling and genetic screening, the challenges of variant interpretation do not outweigh the potential benefits including earlier confirmed diagnosis and possible bespoken therapy.Data availability statement: Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Psychiatry and Mental health
- Clinical Neurology
- Surgery
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Müller, Kathrin
-
Oh, Ki-Wook
-
Nordin, Angelica
-
Panthi, Sudhan
-
Kim, Seung Hyun
-
Nordin, Frida
-
show more...
-
Freischmidt, Axe ...
-
Ludolph, Albert ...
-
Ki, Chang Seok
-
Forsberg, Karin
-
Weishaupt, Joche ...
-
Kim, Young-Eun
-
Andersen, Peter ...
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Neurosciences
- Articles in the publication
-
Journal of Neuro ...
- By the university
-
Umeå University