Fatty aldehyde dehydrogenase: genomic structure, expression and mutation analysis in Sjogren-Larsson syndrome

Fatty aldehyde dehydrogenase (FALDH) is a microsomal enzyme that catalyzes the oxidation of medium- and long-chain aliphatic aldehydes derived from me tabolism of fatty alcohol, phytanic acid, ether glycerolipids and leukotrie ne B4. The FALDH gene (ALDH3A2) in man and mouse consists of 11 exons and i s closely linked to the gene for ALDH3. In both species, alternative splici ng results in formation of a second minor protein, FALDH nu, that has a uni que carboxy-terminal end. The functional significance of this alternate pro tein is not known. In humans, mutations in the FALDH gene cause Sogren-Lars son syndrome (SLS), which is characterized by ichthyosis, mental retardatio n and spasticity. Missense mutations involving 24 amino acid positions in F ALDH have been identified. These amino acids are more highly conserved amon g related class 3 aldehyde dehydrogenase enzymes than expected, suggesting that they are critically important for protein folding, catalysis or stabil ity. Studies of mutations in SLS should prove useful for understanding stru cture-function correlations-in FALDH and other aldehyde dehydrogenase prote ins. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.