GENOMIC ORGANIZATION AND EXPRESSION OF THE HUMAN FATTY ALDEHYDE DEHYDROGENASE GENE (FALDH)

Mutations in the fatty aldehyde dehydrogenase (FALDH) gene cause Sjogr en-Larsson syndrome (SLS)-a disease characterized by mental retardatio n, spasticity, and congenital ichthyosis. To facilitate mutation analy sis in SLS and to study the pathogenesis of FALDH deficiency, we have determined the structural organization and characterized expression of the FALDH (proposed designation ALDH10) gene. The gene consists of 10 exons spanning about 30.5 kb. A TATA-less promoter is associated with the major transcription initiation site found to be 258 bp upstream o f the ATG codon The GC-rich sequences surrounding the transcription in itiation site encompassed regulatory elements that interacted with pro teins in HeLa nuclear extracts and were able to promote transcription in vitro. FALDH is widely expressed as three transcripts of 2, 3.8, an d 4.0 kb, which originate from multiple polyadenylation signals in the 3' UTR. An alternatively spliced mRNA was detected that contains an e xtra exon and encodes an enzyme that is likely to have altered membran e-binding properties. The FALDH gene lies only 50-85 kb hom ALDH3, an aldehyde dehydrogenase gene that has homologous sequence and intron/ex on structure. (C) 1997 Academic Press