Discovery of a novel homozygous SOD1 truncating variant bolsters infantile SOD1 deficiency syndrome
| dc.contributor.author | Doğan, Mustafa | |
| dc.contributor.author | Teralı, Kerem | |
| dc.contributor.author | Eröz, Recep | |
| dc.contributor.author | Kılıç, Hüseyin | |
| dc.contributor.author | Gezdirici, Alper | |
| dc.contributor.author | Gönüllü, Burçin | |
| dc.date.accessioned | 2024-07-01T06:29:08Z | |
| dc.date.available | 2024-07-01T06:29:08Z | |
| dc.date.issued | 2024 | |
| dc.department | Tıp Fakültesi | |
| dc.description.abstract | Superoxide dismutase 1 (SOD1) is an important antioxidant enzyme whose main function is to neutralise superoxide free radicals in the cytoplasm. Heterozygous variants in SOD1 are responsible for a substantial percentage of familial amyotrophic lateral sclerosis (ALS) cases. Recently, several reports have shown that biallelic loss of SOD1 function results in a novel phenotype called infantile SOD1 deficiency syndrome, which is consistent with a recessive pattern of inheritance and can be distinguished from typical (adult-onset) ALS. Methods: We documented detailed family histories and clinical data, followed by whole-exome sequencing and family co-segregation analysis through Sanger sequencing. To facilitate comparisons, relevant data from fifteen previously reported patients with SOD1-related neurodevelopmental disorders were included. Results: This study presents a new Turkish family with two affected children exhibiting severe delayed motor development, infancy-onset loss of motor skills, axial hypotonia, tetraspasticity, and impaired cognitive functions. Genetic analysis revealed a novel homozygous frameshift variant in SOD1 (c.248dupG [p.Asp84Argfs*8]), with computational biochemical studies shedding light on the mechanistic aspects of SOD1 dysfunction. Conclusions: Our findings contribute an affirmative report of a fourth biallelic variant resulting in a severe clinical phenotype, reminiscent of those induced by previously identified homozygous loss-of-function SOD1 variants. This research not only advances our understanding of the pathogenesis of this debilitating neurological syndrome but also aligns with ongoing intensive efforts to comprehend and address SOD1-linked ALS. | |
| dc.identifier.issn | 0301-4851 | |
| dc.identifier.issue | 1 | en_US |
| dc.identifier.scopusquality | Q2 | |
| dc.identifier.uri | https:/dx.doi.org/10.1007/s11033-024-09513-6 | |
| dc.identifier.uri | https://hdl.handle.net/20.500.12451/11999 | |
| dc.identifier.volume | 51 | en_US |
| dc.identifier.wosquality | N/A | |
| dc.indekslendigikaynak | Web of Science | |
| dc.indekslendigikaynak | Scopus | |
| dc.indekslendigikaynak | PubMed | |
| dc.language.iso | en | |
| dc.publisher | Springer Science and Business Media B.V. | |
| dc.relation.ispartof | Molecular Biology Reports | |
| dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | |
| dc.rights | info:eu-repo/semantics/embargoedAccess | |
| dc.subject | Axial Hypotonia | |
| dc.subject | Loss of Motor Skills | |
| dc.subject | Non-amyotrophic Lateral Sclerosis | |
| dc.subject | SOD1 Deficiency | |
| dc.subject | Tetraspasticity | |
| dc.title | Discovery of a novel homozygous SOD1 truncating variant bolsters infantile SOD1 deficiency syndrome | |
| dc.type | Article |
