Sjögren-Larsson syndrome: Diversity of mutations and polymorphisms in the fatty aldehyde dehydrogenase gene (ALDH3A2)

William B. Rizzo, Gael Carney

Research output: Contribution to journalReview articlepeer-review

103 Scopus citations


Sjögren-Larsson syndrome (SLS) is an autosomal recessive disorder characterized by ichthyosis, mental retardation, and spastic diplegia or tetraplegia. The disease is caused by mutations in the ALDH3A2 gene (also known as FALDH and ALDH10) on chromosome 17p11.2 that encodes fatty aldehyde dehydrogenase (FALDH), an enzyme that catalyzes the oxidation of long-chain aldehydes derived from lipid metabolism. In SLS patients, 72 mutations have been identified, with a distribution that is scattered throughout the ALDH3A2 gene. Most mutations are private but several common mutations have been detected, which probably reflect founder effects or recurrent mutational events. Missense mutations comprise the most abundant class (38%) and expression studies indicate that most of these result in a profound reduction in enzyme activity. Deletions account for about 25% of the mutations and range from single nucleotides to entire exons. Twelve splice-site mutations have been demonstrated to cause aberrant splicing in cultured fibroblasts. To date, more than a dozen intragenic ALDH3A2 polymorphisms consisting of SNPs and one microsatellite marker have been characterized, although none of them alter the FALDH protein sequence. The striking mutational diversity in SLS offers a challenge for DNA-based diagnosis, but promises to provide a wealth of information about enzyme structure-function correlations.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalHuman mutation
Issue number1
StatePublished - Jul 2005


  • ALDH3A2
  • Aldehyde dehydrogenase
  • Fatty alcohol
  • Fatty-aldehyde
  • Ichthyosis
  • Mental retardation
  • SLS
  • Spasticity

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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