A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis

dc.contributor.authorNishimura, A. L.
dc.contributor.authorMitne-Neto, Miguel
dc.contributor.authorSilva, Helga Cristina Almeida da [UNIFESP]
dc.contributor.authorRichieri-Costa, Antonio
dc.contributor.authorMiddleton, S.
dc.contributor.authorCascio, D.
dc.contributor.authorKok, F.
dc.contributor.authorOliveira, Joao Ricardo Mendes de
dc.contributor.authorGillingwater, T.
dc.contributor.authorWebb, J.
dc.contributor.authorSkehel, P.
dc.contributor.authorZatz, Mayana
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Edinburgh
dc.contributor.institutionUniv Calif Los Angeles
dc.description.abstractMotor neuron diseases (MNDs) are a group of neurodegenerative disorders with involvement of upper and/or lower motor neurons, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), progressive bulbar palsy, and primary lateral sclerosis. Recently, we have mapped a new locus for an atypical form of ALS/MND ( atypical amyotrophic lateral sclerosis [ALS8]) at 20q13.3 in a large white Brazilian family. Here, we report the finding of a novel missense mutation in the vesicle-associated membrane protein/synaptobrevin-associated membrane protein B (VAPB) gene in patients from this family. Subsequently, the same mutation was identified in patients from six additional kindreds but with different clinical courses, such as ALS8, late-onset SMA, and typical severe ALS with rapid progression. Although it was not possible to link all these families, haplotype analysis suggests a founder effect. Members of the vesicle-associated proteins are intracellular membrane proteins that can associate with microtubules and that have been shown to have a function in membrane transport. These data suggest that clinically variable MNDs may be caused by a dysfunction in intracellular membrane trafficking.en
dc.description.affiliationUniv São Paulo, Inst Biociencias, Dept Biol, Human Genome Res Ctr, São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Sch Med, Anesthesiol Pain & Intens Care Dept, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Hosp Rehabil Craniofacial Anomalies, Genet Serv, Bauru, Brazil
dc.description.affiliationUniv Edinburgh, Dept Neurosci, Edinburgh, Midlothian, Scotland
dc.description.affiliationUniv Calif Los Angeles, Dept Energy, Inst Mol Biol, Inst Genom & Proteom, Los Angeles, CA USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Sch Med, Anesthesiol Pain & Intens Care Dept, São Paulo, Brazil
dc.description.provenanceMade available in DSpace on 2016-01-24T12:37:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2004-11-01. Added 1 bitstream(s) on 2016-01-31T13:33:13Z : No. of bitstreams: 1 WOS000224303500007.pdf: 518642 bytes, checksum: 50d2aca0624569ffaa1b67ae747aa237 (MD5)en
dc.description.sourceWeb of Science
dc.identifier.citationAmerican Journal of Human Genetics. Chicago: Univ Chicago Press, v. 75, n. 5, p. 822-831, 2004.
dc.publisherUniv Chicago Press
dc.relation.ispartofAmerican Journal of Human Genetics
dc.rightsAcesso aberto
dc.titleA mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosisen
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