RESTORATION OF PHYTANIC ACID OXIDATION IN REFSUM-DISEASE FIBROBLASTS FROM PATIENTS WITH MUTATIONS IN THE PHYTANOYL-COA HYDROXYLASE GENE

Refsum disease (RD) is biochemically characterized by the excessive ac cumulation of phytanic acid in tissues and body fluids due to deficien cy of phytanoyl-CoA hydroxylase (PAHX). In this study, we screened thr ee RD patients and identified a novel deletion (88 amino acids), and a missense mutation (Arg275Trp) in the previously reported PAHX cCNA (J ansen et al,, 1997; Mihalik et al,, 1997), Moreover, transfection of s kin fibroblasts from two RD patients with wild-type PAHX gene restored the activity for a-oxidation of phytanic acid. Southern analysis on a somatic cell hybrid panel detected the PAHX gene on chromosome 10, co rroborating radiation hybrid and homozygosity mapping data (Mihalik et al,, 1997; Nadal et al,, 1995). (C) 1998 Federation of European Bioch emical Societies.