Objectives: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by degeneration of motor neurons determining progressive muscular atrophy, weakness, and death from respiratory failure. Methods: Here, we report clinical and molecular findings of a novel Iranian family affected with a severe form of early-onset familial ALS. Results: Three siblings born to consanguineous parents developed a form of ALS characterized by early-onset lower limb involvement and a fast progression, proving fatal at age 16 years for 1 of them. Molecular analysis of the SOD1 gene revealed the homozygous substitution c.434T>C in exon 5 resulting in the amino acid change p.Leu144Ser (L144S), previously reported as a dominant variant. Both parents were heterozygous carriers. The probands' mother recently developed a late-onset ALS with predominant upper motor neuron involvement. Discussion: This report adds p.L144S to the short list of homozygous SOD1 variants and suggests that the development of an earlier-onset and/or faster disease progression can occur when 2 mutated alleles are present.
Homozygous SOD1 Variation L144S Produces a Severe Form of Amyotrophic Lateral Sclerosis in an Iranian Family / D. Gagliardi, M. Ahmadinejad, R. Del Bo, M. Meneri, G.P. Comi, S. Corti, D. Ronchi. - In: NEUROLOGY. GENETICS. - ISSN 2376-7839. - 8:1(2022 Feb), pp. e645.1-e645.4. [10.1212/NXG.0000000000000645]
Homozygous SOD1 Variation L144S Produces a Severe Form of Amyotrophic Lateral Sclerosis in an Iranian Family
D. GagliardiPrimo
;R. Del Bo;M. Meneri;G.P. Comi;S. CortiPenultimo
;D. Ronchi
Ultimo
2022
Abstract
Objectives: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by degeneration of motor neurons determining progressive muscular atrophy, weakness, and death from respiratory failure. Methods: Here, we report clinical and molecular findings of a novel Iranian family affected with a severe form of early-onset familial ALS. Results: Three siblings born to consanguineous parents developed a form of ALS characterized by early-onset lower limb involvement and a fast progression, proving fatal at age 16 years for 1 of them. Molecular analysis of the SOD1 gene revealed the homozygous substitution c.434T>C in exon 5 resulting in the amino acid change p.Leu144Ser (L144S), previously reported as a dominant variant. Both parents were heterozygous carriers. The probands' mother recently developed a late-onset ALS with predominant upper motor neuron involvement. Discussion: This report adds p.L144S to the short list of homozygous SOD1 variants and suggests that the development of an earlier-onset and/or faster disease progression can occur when 2 mutated alleles are present.File | Dimensione | Formato | |
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