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@ARTICLE{Fahmy:169125,
author = {Fahmy, Nagia and Müller, Kathrin and Andersen, Peter Munch
and Marklund, Stefan L and Otto, Markus and Ludolph, Albert
and Hamdi, Nabila},
title = {{A} novel homozygous p.{S}er69{P}ro {SOD}1 mutation causes
severe young-onset {ALS} with decreased enzyme activity.},
journal = {Journal of neurology},
volume = {270},
number = {3},
issn = {0340-5354},
address = {Berlin},
publisher = {Springer},
reportid = {DZNE-2023-00004},
pages = {1770-1773},
year = {2023},
note = {ISSN 1432-1459 not unique: **2 hits**.},
abstract = {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.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.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).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.},
keywords = {Humans / Superoxide Dismutase-1: genetics / Amyotrophic
Lateral Sclerosis: genetics / Amyotrophic Lateral Sclerosis:
diagnosis / Mutation / Homozygote / Motor Neurons /
Superoxide Dismutase: genetics / Superoxide Dismutase-1 (NLM
Chemicals) / Enzyme activity (Other) / Homozygous (Other) /
Novel mutation (Other) / SOD1 (Other) / Young-onset (Other)
/ Superoxide Dismutase (NLM Chemicals) / SOD1 protein, human
(NLM Chemicals)},
cin = {Clinical Study Center Ulm},
ddc = {610},
cid = {I:(DE-2719)5000077},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC9971132},
pubmed = {pmid:36472686},
doi = {10.1007/s00415-022-11489-x},
url = {https://pub.dzne.de/record/169125},
}