A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis.
In: American journal of human genetics, Jg. 75 (2004-11-01), Heft 5, S. 822-31
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Zugriff:
Motor 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.
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A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis.
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Autor/in / Beteiligte Person: | Nishimura, AL ; Mitne-Neto, M ; Silva, HC ; Richieri-Costa, A ; Middleton, S ; Cascio, D ; Kok, F ; Oliveira, JR ; Gillingwater, T ; Webb, J ; Skehel, P ; Zatz, M |
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Zeitschrift: | American journal of human genetics, Jg. 75 (2004-11-01), Heft 5, S. 822-31 |
Veröffentlichung: | 2008- : [Cambridge, MA] : Cell Press ; <i>Original Publication</i>: Baltimore, American Society of Human Genetics., 2004 |
Medientyp: | academicJournal |
ISSN: | 0002-9297 (print) |
DOI: | 10.1086/425287 |
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