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Article: A Missense Mutation in SLC33A1, which Encodes the Acetyl-CoA Transporter, Causes Autosomal-Dominant Spastic Paraplegia (SPG42)
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TitleA Missense Mutation in SLC33A1, which Encodes the Acetyl-CoA Transporter, Causes Autosomal-Dominant Spastic Paraplegia (SPG42)
 
AuthorsLin, P4
Li, J4
Liu, Q4
Mao, F4
Li, J4
Qiu, R4
Hu, H4
Song, Y4
Yang, Y4
Gao, G4
Yan, C3
Yang, W2 4
Shao, C1 4
Gong, Y4
 
Issue Date2008
 
PublisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/
 
CitationAmerican Journal Of Human Genetics, 2008, v. 83 n. 6, p. 752-759 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.ajhg.2008.11.003
 
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.
 
ISSN0002-9297
2013 Impact Factor: 10.987
 
DOIhttp://dx.doi.org/10.1016/j.ajhg.2008.11.003
 
ISI Accession Number IDWOS:000261822100010
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLin, P
 
dc.contributor.authorLi, J
 
dc.contributor.authorLiu, Q
 
dc.contributor.authorMao, F
 
dc.contributor.authorLi, J
 
dc.contributor.authorQiu, R
 
dc.contributor.authorHu, H
 
dc.contributor.authorSong, Y
 
dc.contributor.authorYang, Y
 
dc.contributor.authorGao, G
 
dc.contributor.authorYan, C
 
dc.contributor.authorYang, W
 
dc.contributor.authorShao, C
 
dc.contributor.authorGong, Y
 
dc.date.accessioned2010-05-31T03:51:51Z
 
dc.date.available2010-05-31T03:51:51Z
 
dc.date.issued2008
 
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.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationAmerican Journal Of Human Genetics, 2008, v. 83 n. 6, p. 752-759 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.ajhg.2008.11.003
 
dc.identifier.doihttp://dx.doi.org/10.1016/j.ajhg.2008.11.003
 
dc.identifier.epage759
 
dc.identifier.hkuros155943
 
dc.identifier.isiWOS:000261822100010
 
dc.identifier.issn0002-9297
2013 Impact Factor: 10.987
 
dc.identifier.issue6
 
dc.identifier.pmid19061983
 
dc.identifier.scopuseid_2-s2.0-57649084368
 
dc.identifier.spage752
 
dc.identifier.urihttp://hdl.handle.net/10722/59518
 
dc.identifier.volume83
 
dc.languageeng
 
dc.publisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofAmerican Journal of Human Genetics
 
dc.relation.referencesReferences in Scopus
 
dc.titleA Missense Mutation in SLC33A1, which Encodes the Acetyl-CoA Transporter, Causes Autosomal-Dominant Spastic Paraplegia (SPG42)
 
dc.typeArticle
 
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Author Affiliations
  1. Rutgers, The State University of New Jersey
  2. The University of Hong Kong
  3. Qilu Hospital of Shandong University
  4. Ministry of Education China