Discovery of a novel homozygous SOD1 truncating variant bolsters infantile SOD1 deficiency syndrome.
Mol Biol Rep
; 51(1): 580, 2024 Apr 26.
Article
en En
| MEDLINE
| ID: mdl-38668754
ABSTRACT
OBJECTIVE:
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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Superóxido Dismutasa-1
/
Esclerosis Amiotrófica Lateral
Límite:
Adolescent
/
Child
/
Female
/
Humans
/
Male
País como asunto:
Asia
Idioma:
En
Año:
2024
Tipo del documento:
Article