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 accumulation of phytanic acid in tissues and body fluids due to deficiency of phytanoyl-CoA hydroxylase (PAHX). In this study, we screened three RD patients and identified a novel deletion (88 amino acids), and a missense mutation (Arg275Trp) in the previously reported PAHX cDNA (Jansen et al., 1997; Mihalik et al., 1997). Moreover, transfection of skin fibroblasts from two RD patients with wild-type PAHX gene restored the activity for alpha-oxidation of phytanic acid. Southern analysis on a somatic cell hybrid panel detected the PAHX gene on chromosome 10, corroborating radiation hybrid and homozygosity mapping data (Mihalik et al., 1997; Nadal et al., 1995).
Chahal
A
A
Department of Pediatrics, Medical University of South Carolina, Charleston 29425, USA.
Khan
M
M
Pai
S G
SG
Barbosa
E
E
Singh
I
I
D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010084:Oxidation-Reduction; D010831:Phytanic Acid / Q000378:metabolism*; D012035:Refsum Disease / Q000201:enzymology* / Q000378:metabolism; D014162:Transfection
D010831:Phytanic Acid; D006899:Mixed Function Oxygenases; C102623:PHYH protein, human