title: SOD1 G93D sporadic amyotrophic lateral sclerosis (SALS) patient with rapid progression and concomitant novel ANG variant.
abstract: SOD1 G93D mutation has been described in amyotrophic lateral sclerosis (ALS) patients with slowly progressive disease. We describe an Italian patient affected by sporadic ALS with the SOD1 G93D mutation that disclosed an unusual rapid progression with death occurring after 30 months from the symptom onset. Considering the atypical clinical course further genes associated with ALS or known to be causative were studied including ANG, PGRN, TARDBP, FUS, VCP, CHRNA3, CHRNA4, and CHRNB4. A novel heterozygous ANG missense variant (c.433 C>T, p.R145C) was identified which is neither reported in controls nor in 1000 genomes and single nucleotide polymorphism (SNP) databases. This report confirms that clinical course of SOD1-related ALS may be modulated by other causative or associated genes, including ANG and suggests that extensive screening of ALS-associated genes in patients with an already identified mutation may be helpful for better knowledge of genetic architecture of ALS.
authors.affiliation: Institute of Neurology, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Luigetti
authors.forename: Serena
authors.initials: S
authors.lastname: Lattante
authors.forename: Marcella
authors.initials: M
authors.lastname: Zollino
authors.forename: Amelia
authors.initials: A
authors.lastname: Conte
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Marangi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Del Grande
authors.forename: Mario
authors.initials: M
authors.lastname: Sabatelli
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis / Q000379:methods; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007558:Italy; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012259:Ribonuclease, Pancreatic / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; C046366:angiogenin; D012259:Ribonuclease, Pancreatic