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

Gael Carney, Shu Wei, William B Rizzo

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Number of pages1
JournalHuman mutation
Volume24
Issue number2
StatePublished - Aug 2004

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long-chain-aldehyde dehydrogenase
Exons
Mutation
Genes
Haplotypes
RNA Splice Sites
Guanine Nucleotides
Sequence Deletion
Insertional Mutagenesis
Amino Acid Substitution
Lipid Metabolism
Introns
Single Nucleotide Polymorphism
Catalytic Domain
Fetus
Fibroblasts
Alleles

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Sjögren-Larsson syndrome : seven novel mutations in the fatty aldehyde dehydrogenase gene ALDH3A2. / Carney, Gael; Wei, Shu; Rizzo, William B.

In: Human mutation, Vol. 24, No. 2, 08.2004.

Research output: Contribution to journalArticle

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