Homozygous <i>SOD1</i> Variation L144S Produces a Severe Form of Amyotrophic Lateral Sclerosis in an Iranian Family
Delia Gagliardi, Minoo Ahmadinejad, Roberto Del Bo, Megi Meneri, Giacomo P. Comi, Stefania Corti, Dario Ronchi
Abstract
<h3>Objectives</h3> 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. <h3>Methods</h3> Here, we report clinical and molecular findings of a novel Iranian family affected with a severe form of early-onset familial ALS. <h3>Results</h3> 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 <i>SOD1</i> 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 probands9 mother recently developed a late-onset ALS with predominant upper motor neuron involvement. <h3>Discussion</h3> This report adds p.L144S to the short list of homozygous <i>SOD1</i> variants and suggests that the development of an earlier-onset and/or faster disease progression can occur when 2 mutated alleles are present.