File(s) not publicly available
New VAPB deletion variant and exclusion of VAPB mutations in familial ALS
journal contribution
posted on 2023-06-08, 13:41 authored by J E Landers, Nigel LeighNigel Leigh, A L Leclerc, L Shi, A Virkud, T Cho, M M Maxwell, A F Henry, M Polack, J D Glass, T J Kwiatkowski, othersOBJECTIVE Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disorder involving upper and lower motor neurons. The vesicle-associated membrane protein B (VAPB) gene has been genetically linked to ALS in several large Brazilian families in which the disorder is caused by a proline to serine mutation at codon 56 (P56S). No additional mutations have been identified. METHODS To establish the prevalence of VAPB mutations, we screened 80 familial ALS samples by DNA sequencing. RESULTS Our study failed to identify any novel VAPB gene mutations but identified a single Brazilian family harboring the P56S mutation. In a second familial ALS case, we identified a three-base pair deletion within exon 5 of the VAPB gene that deleted the serine residue at position 160 (Delta S160). This variant is detected in a normal population at low frequency (0.45%). Analyses of homology alignment and secondary structure predict that this deletion significantly alters the structure of VAPB, although a GFP-Delta S160 VAPB fusion protein demonstrates a wild-type subcellular localization. This contrasts the aberrant localization observed in a GFP-P56S VAPB fusion protein. The allele frequency of Delta S160 in patients with sporadic ALS does not differ significantly from that in the normal population. CONCLUSIONS Mutations in the VAPB gene are rare and the Delta S160 variant does not contribute to the development of amyotrophic lateral sclerosis.
History
Publication status
- Published
Journal
NeurologyISSN
1526-632XPublisher
American Academy of NeurologyIssue
14Volume
70Page range
1179-85Department affiliated with
- Clinical and Experimental Medicine Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-11-14Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC