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Article: Recessive amyotrophic lateral sclerosis families with the D90A SOD1 mutation share a common founder: Evidence for a linked protective factor

TitleRecessive amyotrophic lateral sclerosis families with the D90A SOD1 mutation share a common founder: Evidence for a linked protective factor
Authors
Issue Date1998
PublisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
Citation
Human Molecular Genetics, 1998, v. 7 n. 13, p. 2045-2050 How to Cite?
AbstractAmyotrophic lateral sclerosis (ALS) is a progressive motor neurodegeneration resulting in paralysis and death from respiratory failure within 3-5 years. About 20% of familial cases are associated with mutations in the gene for copper/zinc superoxide dismutase (SOD1), which catalyses the dismutation of the superoxide radical to hydrogen peroxide and oxygen. Experimental evidence suggests mutations act by a toxic gain of function but the mechanism is unknown. There are > 60 known SOD1 mutations associated with ALS and all are dominant except for one in exon 4, a D90A substitution which is recessive. D90A pedigrees with dominant inheritance have now been reported and this apparent contradiction needs to be explained. We performed a worldwide haplotype study on 28 D90A pedigrees using six highly polymorphic microsatellite markers. We now show that all 20 recessive families share the same founder (a = 0.999), regardless of geographical location, whereas several founders exist for the eight dominant families (a = 0.385). This finding confirms that D90A can act in a dominant fashion in keeping with all other SOD1 mutations, but that on one occasion, a new instance of this mutation has been recessive. We propose a tightly linked protective factor which modifies the toxic effect of mutant SOD1 in recessive families.
Persistent Identifierhttp://hdl.handle.net/10722/175984
ISSN
2015 Impact Factor: 5.985
2015 SCImago Journal Rankings: 4.288
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorAlChalabi, Aen_US
dc.contributor.authorAndersen, PMen_US
dc.contributor.authorChioza, Ben_US
dc.contributor.authorShaw, Cen_US
dc.contributor.authorSham, PCen_US
dc.contributor.authorRobberecht, Wen_US
dc.contributor.authorMatthijs, Gen_US
dc.contributor.authorCamu, Wen_US
dc.contributor.authorMarklund, SLen_US
dc.contributor.authorForsgren, Len_US
dc.contributor.authorRouleau, Gen_US
dc.contributor.authorLaing, NGen_US
dc.contributor.authorHurse, PVen_US
dc.contributor.authorSiddique, Ten_US
dc.contributor.authorLeigh, PNen_US
dc.contributor.authorPowell, JFen_US
dc.date.accessioned2012-11-26T09:03:17Z-
dc.date.available2012-11-26T09:03:17Z-
dc.date.issued1998en_US
dc.identifier.citationHuman Molecular Genetics, 1998, v. 7 n. 13, p. 2045-2050en_US
dc.identifier.issn0964-6906en_US
dc.identifier.urihttp://hdl.handle.net/10722/175984-
dc.description.abstractAmyotrophic lateral sclerosis (ALS) is a progressive motor neurodegeneration resulting in paralysis and death from respiratory failure within 3-5 years. About 20% of familial cases are associated with mutations in the gene for copper/zinc superoxide dismutase (SOD1), which catalyses the dismutation of the superoxide radical to hydrogen peroxide and oxygen. Experimental evidence suggests mutations act by a toxic gain of function but the mechanism is unknown. There are > 60 known SOD1 mutations associated with ALS and all are dominant except for one in exon 4, a D90A substitution which is recessive. D90A pedigrees with dominant inheritance have now been reported and this apparent contradiction needs to be explained. We performed a worldwide haplotype study on 28 D90A pedigrees using six highly polymorphic microsatellite markers. We now show that all 20 recessive families share the same founder (a = 0.999), regardless of geographical location, whereas several founders exist for the eight dominant families (a = 0.385). This finding confirms that D90A can act in a dominant fashion in keeping with all other SOD1 mutations, but that on one occasion, a new instance of this mutation has been recessive. We propose a tightly linked protective factor which modifies the toxic effect of mutant SOD1 in recessive families.en_US
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/en_US
dc.relation.ispartofHuman Molecular Geneticsen_US
dc.subject.meshAmino Acid Substitutionen_US
dc.subject.meshAmyotrophic Lateral Sclerosis - Geneticsen_US
dc.subject.meshFamilyen_US
dc.subject.meshFamily Healthen_US
dc.subject.meshFemaleen_US
dc.subject.meshFounder Effecten_US
dc.subject.meshGenes, Recessiveen_US
dc.subject.meshGenetic Linkageen_US
dc.subject.meshHeterozygoteen_US
dc.subject.meshHomozygoteen_US
dc.subject.meshHumansen_US
dc.subject.meshLinkage Disequilibriumen_US
dc.subject.meshLod Scoreen_US
dc.subject.meshMaleen_US
dc.subject.meshMicrosatellite Repeatsen_US
dc.subject.meshMutationen_US
dc.subject.meshPedigreeen_US
dc.subject.meshSuperoxide Dismutase - Geneticsen_US
dc.titleRecessive amyotrophic lateral sclerosis families with the D90A SOD1 mutation share a common founder: Evidence for a linked protective factoren_US
dc.typeArticleen_US
dc.identifier.emailSham, PC: pcsham@hku.hken_US
dc.identifier.authoritySham, PC=rp00459en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1093/hmg/7.13.2045-
dc.identifier.pmid9817920-
dc.identifier.scopuseid_2-s2.0-7844227669en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-7844227669&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume7en_US
dc.identifier.issue13en_US
dc.identifier.spage2045en_US
dc.identifier.epage2050en_US
dc.identifier.isiWOS:000077576700007-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridAlChalabi, A=7003751621en_US
dc.identifier.scopusauthoridAndersen, PM=7403262569en_US
dc.identifier.scopusauthoridChioza, B=6603239784en_US
dc.identifier.scopusauthoridShaw, C=35370282000en_US
dc.identifier.scopusauthoridSham, PC=34573429300en_US
dc.identifier.scopusauthoridRobberecht, W=7005572606en_US
dc.identifier.scopusauthoridMatthijs, G=7006089830en_US
dc.identifier.scopusauthoridCamu, W=7003581532en_US
dc.identifier.scopusauthoridMarklund, SL=8880532400en_US
dc.identifier.scopusauthoridForsgren, L=7004809205en_US
dc.identifier.scopusauthoridRouleau, G=36042364200en_US
dc.identifier.scopusauthoridLaing, NG=7005008313en_US
dc.identifier.scopusauthoridHurse, PV=7801589823en_US
dc.identifier.scopusauthoridSiddique, T=7004493828en_US
dc.identifier.scopusauthoridLeigh, PN=26643325600en_US
dc.identifier.scopusauthoridPowell, JF=7403541196en_US

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