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Sjögren-Larsson syndrome: Seven novel mutations in the fatty aldehyde dehydrogenase gene ALDH3A2

2004; Wiley; Volume: 24; Issue: 2 Linguagem: Inglês

10.1002/humu.9262

1098-1004

Gael Carney, S.Jack Wei, William B. Rizzo,

Lipid metabolism and biosynthesis

Human MutationVolume 24, Issue 2 p. 186-186 Mutation in BriefFree Access Sjögren-Larsson syndrome: Seven novel mutations in the fatty aldehyde dehydrogenase gene ALDH3A2†‡ Gael Carney, Gael Carney Department of Pediatrics and Munroe-Meyer Institute, University of Nebraska Medical Center and Hobart Wiltse Center for the Study of Metabolic Disorders, Children's Hospital of Omaha, Omaha, NebraskaSearch for more papers by this authorShu Wei, Shu Wei Department of Pediatrics and Munroe-Meyer Institute, University of Nebraska Medical Center and Hobart Wiltse Center for the Study of Metabolic Disorders, Children's Hospital of Omaha, Omaha, NebraskaSearch for more papers by this authorWilliam B. Rizzo, Corresponding Author William B. Rizzo wrizzo@unmc.edu Department of Pediatrics and Munroe-Meyer Institute, University of Nebraska Medical Center and Hobart Wiltse Center for the Study of Metabolic Disorders, Children's Hospital of Omaha, Omaha, NebraskaDepartment of Pediatrics, University of Nebraska Medical Center, 985456 Nebraska Medical Center, Omaha, NE 68198-5456Search for more papers by this author Gael Carney, Gael Carney Department of Pediatrics and Munroe-Meyer Institute, University of Nebraska Medical Center and Hobart Wiltse Center for the Study of Metabolic Disorders, Children's Hospital of Omaha, Omaha, NebraskaSearch for more papers by this authorShu Wei, Shu Wei Department of Pediatrics and Munroe-Meyer Institute, University of Nebraska Medical Center and Hobart Wiltse Center for the Study of Metabolic Disorders, Children's Hospital of Omaha, Omaha, NebraskaSearch for more papers by this authorWilliam B. Rizzo, Corresponding Author William B. Rizzo wrizzo@unmc.edu Department of Pediatrics and Munroe-Meyer Institute, University of Nebraska Medical Center and Hobart Wiltse Center for the Study of Metabolic Disorders, Children's Hospital of Omaha, Omaha, NebraskaDepartment of Pediatrics, University of Nebraska Medical Center, 985456 Nebraska Medical Center, Omaha, NE 68198-5456Search for more papers by this author First published: 30 June 2004 https://doi.org/10.1002/humu.9262Citations: 20 † Communicated by Elizabeth Neufeld ‡ Online Citation: Human Mutation, Mutation in Brief #733 (2004) Onlinehttp://www3.interscience.wiley.com/homepages/38515/pdf/733.pdf AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Sjögren-Larsson syndrome (SLS) is an inherited neurocutaneous disease caused by mutations in the ALDH3A2 gene that codes for fatty aldehyde dehydrogenase (FALDH), an enzyme involved in lipid metabolism. We performed mutation analysis in probands or fetuses from 13 unrelated SLS families and identified seven novel ALDH3A2 mutations. Two mutations involved an insertion or deletion of a single guanine nucleotide at the same position in exon 9: c.1223delG and c.1223_1224insG. A 66-bp duplication in exon 2 probably arose from unequal crossing over within a mispaired 10-bp sequence that is normally repeated within the exon. Based on RT-PCR of fibroblast RNA, the c.1107+2T>G donor splice-site mutation in intron 7 produced two mRNA transcripts, one skipping exon 7 and the other skipping exons 6–8. Expression of the c.1139G>A mutation in exon 8, which is predicted to cause an amino acid substitution (Ser380Asn) in an evolutionarily conserved region of the FALDH catalytic domain, resulted in a protein with profoundly reduced enzymatic activity. By analyzing single nucleotide polymorphisms within the ALDH3A2 gene, we detected four different haplotypes among the new mutant alleles. These results demonstrate a rich diversity of mutations and haplotype associations in SLS. © 2004 Wiley-Liss, Inc. Citing Literature Volume24, Issue2August 2004Pages 186-186 RelatedInformation