Comprehensive analysis to explain reduced or increased SOD1 enzymatic activity in erythrocytes in ALS patients and their relatives

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Our objective was to in blood samples from 3723 individuals including ALS patients without a coding SOD1 mutation and 372 control individuals characterize stabilities of mutant SOD1s, compare SOD1 enzymatic activities between patients with different genetic causes of ALS, and search for underlying causes of deviant SOD1 activities in individuals lacking SOD1 mutations. Erythrocyte SOD1 enzymatic activities normalized to hemoglobin content were determined. Coding SOD1 sequences were analyzed by Sanger sequencing, copy number variations by fragment length analysis and by TaqMan Assay. Hemoglobin disorders were searched for. Of the 46 SOD1 mutations found, ¾ caused severe destabilization of the mutant protein but in ¼ SOD1 was essentially physically stable. Mutations producing structural changes all caused halved SOD activities. There were no differences in SOD1 activities between controls and patients without any detected SOD1 mutations or patients with C9ORF72HRE or TBK1 mutations. In the low and high SOD1 activity groups no deviations were found in exon copy numbers and intron gross structures. Also, no uncommon variants in exon-flanking sequences were detected. Thalassemias and iron deficiency anemia were associated with increased SOD1 activity/hemoglobin ratios. In conclusion, adjunct erythrocyte SOD activity analysis is of value to signal the presence of exon and splice-site-intron mutations that influence the SOD1 structure.

Birve, AnnaUmeå universitet,Klinisk neurovetenskap(Swepub:umu)anbi0001 (författare)
Berdynski, MariuszUmeå universitet,Klinisk neurovetenskap(Swepub:umu)mabe0489 (författare)
Hjertkvist, KarinUmeå universitet,Institutionen för medicinsk biovetenskap(Swepub:umu)kahj0001 (författare)
Rofougaran, RezaUmeå universitet,Klinisk neurovetenskap(Swepub:umu)rearon05 (författare)
Nilsson, Torbjörn K.Umeå universitet,Institutionen för medicinsk biovetenskap(Swepub:umu)toni0049 (författare)
Glass, Jonathan D. (författare)
Marklund, Stefan L.Umeå universitet,Institutionen för medicinsk biovetenskap(Swepub:umu)stma0003 (författare)
Andersen, Peter M.Umeå universitet,Klinisk neurovetenskap(Swepub:umu)pean0001 (författare)
Umeå universitetKlinisk neurovetenskap (creator_code:org_t)

Av författaren/redakt...: Keskin, Isil, 19 ...; Birve, Anna; Berdynski, Mariu ...; Hjertkvist, Kari ...; Rofougaran, Reza; Nilsson, Torbjör ...; visa fler...; Glass, Jonathan ...; Marklund, Stefan ...; Andersen, Peter ...; visa färre...

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