title: Sporadic ALS is not associated with VAPB gene mutations in Southern Italy.
abstract: Mutations in the Cu/Zn superoxide dismutase (Sod1) gene have been reported to cause adult-onset autosomal dominant Amyotrophic Lateral Sclerosis (FALS). In sporadic cases (SALS) de novo mutations in the Sod1 gene have occasionally been observed. The recent finding of a mutation in the VAMP/synaptobrevin-associated membrane protein B (VAPB) gene as the cause of amyotrophic lateral sclerosis (ALS8), prompted us to investigate the entire coding region of this gene in SALS patients. One hundred twenty-five unrelated patients with adult-onset ALS and 150 healthy sex-age-matched subjects with the same genetic background were analyzed. Genetic analysis for all exons of the VAPB gene by DHPLC revealed 5 variant profiles in 83 out of 125 SALS patients. Direct sequencing of these PCR products revealed 3 nucleotide substitutions. Two of these were found within intron 3 of the gene, harbouring 4 variant DHPLC profiles. The third nucleotide variation (Asp130Glu) was the only substitution present in the coding region of the VAPB gene, and it occurred within exon 4. It was found in three patients out of 125. The frequency of the detected exon variation in the VAPB gene was not significantly different between patients and controls. In conclusion, our study suggests that VAPB mutations are not a common cause of adult-onset SALS.
authors.affiliation: Institute of Neurological Sciences, National Research Council, Mangone, Cosenza, Italy. fl.conforti@isn.cnr.it
authors.forename: Francesca Luisa
authors.initials: FL
authors.lastname: Conforti
authors.forename: Teresa
authors.initials: T
authors.lastname: Sprovieri
authors.forename: Rosalucia
authors.initials: R
authors.lastname: Mazzei
authors.forename: Carmine
authors.initials: C
authors.lastname: Ungaro
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tessitore
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Tedeschi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Patitucci
authors.forename: Angela
authors.initials: A
authors.lastname: Magariello
authors.forename: Annalia
authors.initials: A
authors.lastname: Gabriele
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Labella
authors.forename: Isabella Laura
authors.initials: IL
authors.lastname: Simone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Majorana
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Monsurrò
authors.forename: Paola
authors.initials: P
authors.lastname: Valentino
authors.forename: Maria
authors.initials: M
authors.lastname: Muglia
authors.forename: Aldo
authors.initials: A
authors.lastname: Quattrone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D001224:Aspartic Acid; D001483:Base Sequence; D016022:Case-Control Studies; D005091:Exons; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D018698:Glutamic Acid; D006801:Humans; D007438:Introns; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: C496748:VAPB protein, human; D033921:Vesicular Transport Proteins; D001224:Aspartic Acid; D018698:Glutamic Acid