Sporadic ALS is not associated with VAPB gene mutations in Southern Italy.
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.
Conforti
Francesca Luisa
FL
Institute of Neurological Sciences, National Research Council, Mangone, Cosenza, Italy. fl.conforti@isn.cnr.it
Sprovieri
Teresa
T
Mazzei
Rosalucia
R
Ungaro
Carmine
C
Tessitore
Alessandro
A
Tedeschi
Gioacchino
G
Patitucci
Alessandra
A
Magariello
Angela
A
Gabriele
Annalia
A
Labella
Vincenzo
V
Simone
Isabella Laura
IL
Majorana
Giovanni
G
Monsurrò
Maria Rosaria
MR
Valentino
Paola
P
Muglia
Maria
M
Quattrone
Aldo
A
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*
C496748:VAPB protein, human; D033921:Vesicular Transport Proteins; D001224:Aspartic Acid; D018698:Glutamic Acid