File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: A Missense Mutation in SLC33A1, which Encodes the Acetyl-CoA Transporter, Causes Autosomal-Dominant Spastic Paraplegia (SPG42)

TitleA Missense Mutation in SLC33A1, which Encodes the Acetyl-CoA Transporter, Causes Autosomal-Dominant Spastic Paraplegia (SPG42)
Authors
Issue Date2008
PublisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/
Citation
American Journal Of Human Genetics, 2008, v. 83 n. 6, p. 752-759 How to Cite?
AbstractHereditary spastic paraplegias (HSPs), characterized by progressive and bilateral spasticity of the legs, are usually caused by developmental failure or degeneration of motor axons in the corticospinal tract. There are considerable interfamilial and intrafamilial variations in age at onset and severity of spasticity. Genetic studies also showed that there are dozens of genetic loci, on multiple chromosomes, that are responsible for HSPs. Through linkage study of a pedigree of HSP with autosomal-dominant inheritance, we mapped the causative gene to 3q24-q26. Screening of candidate genes revealed that the HSP is caused by a missense mutation in the gene for acetyl-CoA transporter (SLC33A1). It is predicted that the missense mutation, causing the change of the highly conserved serine to arginine at the codon 113 (p. S113R), disrupts the second transmembrane domain in the transporter and reverses the orientation of all of the descending domains. Knockdown of Slc33a1 in zebrafish caused a curve-shaped tail and defective axon outgrowth from the spinal cord. Although the wild-type human SLC33A1 was able to rescue the phenotype caused by Slc33a1 knockdown in zebrafish, the mutant SLC33A1 (p.S113R) was not, suggesting that S113R mutation renders SLC33A1 nonfunctional and one that wild-type allele is not sufficient for sustaining the outgrowth and maintenance of long motor axons in human heterozygotes. Thus, our study illustrated a critical role of acetyl-CoA transporter in motor-neuron development and function. © 2008 The American Society of Human Genetics.
Persistent Identifierhttp://hdl.handle.net/10722/59518
ISSN
2015 Impact Factor: 10.794
2015 SCImago Journal Rankings: 8.769
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLin, Pen_HK
dc.contributor.authorLi, Jen_HK
dc.contributor.authorLiu, Qen_HK
dc.contributor.authorMao, Fen_HK
dc.contributor.authorLi, Jen_HK
dc.contributor.authorQiu, Ren_HK
dc.contributor.authorHu, Hen_HK
dc.contributor.authorSong, Yen_HK
dc.contributor.authorYang, Yen_HK
dc.contributor.authorGao, Gen_HK
dc.contributor.authorYan, Cen_HK
dc.contributor.authorYang, Wen_HK
dc.contributor.authorShao, Cen_HK
dc.contributor.authorGong, Yen_HK
dc.date.accessioned2010-05-31T03:51:51Z-
dc.date.available2010-05-31T03:51:51Z-
dc.date.issued2008en_HK
dc.identifier.citationAmerican Journal Of Human Genetics, 2008, v. 83 n. 6, p. 752-759en_HK
dc.identifier.issn0002-9297en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59518-
dc.description.abstractHereditary spastic paraplegias (HSPs), characterized by progressive and bilateral spasticity of the legs, are usually caused by developmental failure or degeneration of motor axons in the corticospinal tract. There are considerable interfamilial and intrafamilial variations in age at onset and severity of spasticity. Genetic studies also showed that there are dozens of genetic loci, on multiple chromosomes, that are responsible for HSPs. Through linkage study of a pedigree of HSP with autosomal-dominant inheritance, we mapped the causative gene to 3q24-q26. Screening of candidate genes revealed that the HSP is caused by a missense mutation in the gene for acetyl-CoA transporter (SLC33A1). It is predicted that the missense mutation, causing the change of the highly conserved serine to arginine at the codon 113 (p. S113R), disrupts the second transmembrane domain in the transporter and reverses the orientation of all of the descending domains. Knockdown of Slc33a1 in zebrafish caused a curve-shaped tail and defective axon outgrowth from the spinal cord. Although the wild-type human SLC33A1 was able to rescue the phenotype caused by Slc33a1 knockdown in zebrafish, the mutant SLC33A1 (p.S113R) was not, suggesting that S113R mutation renders SLC33A1 nonfunctional and one that wild-type allele is not sufficient for sustaining the outgrowth and maintenance of long motor axons in human heterozygotes. Thus, our study illustrated a critical role of acetyl-CoA transporter in motor-neuron development and function. © 2008 The American Society of Human Genetics.en_HK
dc.languageengen_HK
dc.publisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/en_HK
dc.relation.ispartofAmerican Journal of Human Geneticsen_HK
dc.titleA Missense Mutation in SLC33A1, which Encodes the Acetyl-CoA Transporter, Causes Autosomal-Dominant Spastic Paraplegia (SPG42)en_HK
dc.typeArticleen_HK
dc.identifier.emailYang, W:yangwl@hkucc.hku.hken_HK
dc.identifier.authorityYang, W=rp00524en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.ajhg.2008.11.003en_HK
dc.identifier.pmid19061983-
dc.identifier.scopuseid_2-s2.0-57649084368en_HK
dc.identifier.hkuros155943en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-57649084368&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume83en_HK
dc.identifier.issue6en_HK
dc.identifier.spage752en_HK
dc.identifier.epage759en_HK
dc.identifier.isiWOS:000261822100010-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLin, P=37022502300en_HK
dc.identifier.scopusauthoridLi, J=35345136800en_HK
dc.identifier.scopusauthoridLiu, Q=7406292285en_HK
dc.identifier.scopusauthoridMao, F=36514971400en_HK
dc.identifier.scopusauthoridLi, J=36016939200en_HK
dc.identifier.scopusauthoridQiu, R=25923977400en_HK
dc.identifier.scopusauthoridHu, H=24280551300en_HK
dc.identifier.scopusauthoridSong, Y=10141178900en_HK
dc.identifier.scopusauthoridYang, Y=16481518700en_HK
dc.identifier.scopusauthoridGao, G=7403170805en_HK
dc.identifier.scopusauthoridYan, C=7401746616en_HK
dc.identifier.scopusauthoridYang, W=23101349500en_HK
dc.identifier.scopusauthoridShao, C=7102817023en_HK
dc.identifier.scopusauthoridGong, Y=7402473493en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats