Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene

Refsum disease is an autosomal-recessively inherited disorder characterized clinically by a tetrad of abnormalities: retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia and elevated protein levels in the cerebrospinal fluid (CSF) without an increase in the number of cells in the CSF. All...

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Bibliographic Details
Published in:	Nature genetics Vol. 17; no. 2; pp. 190 - 193
Main Authors:	Jansen, Gerbert A, Oftnan, Rob, Ferdinandusse, Sacha, Ijlst, Lodewijk, Muijsers, Anton O, Skjeldal, Ola H, Stokke, Oddvar, Jakobs, Cornells, Besley, Guy T.N, Wraith, J. Ed, Wanders, Ronald J.A
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group 01-10-1997
Subjects:	Adult Amino Acid Sequence Animals Base Sequence Biological and medical sciences Case-Control Studies Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction DNA Primers - genetics DNA, Complementary - genetics Female Gene Expression Humans Infant Liver - enzymology Male Medical sciences Microbodies - enzymology Mixed Function Oxygenases - genetics Mixed Function Oxygenases - isolation & purification Molecular Sequence Data Mutation Nervous system (semeiology, syndromes) Neurology Point Mutation Polymerase Chain Reaction Rats Refsum Disease - enzymology Refsum Disease - genetics Sequence Deletion Human Nervous system diseases Nucleotide sequence Metabolic diseases Homology Molecular interaction Lipids Molecular targeting Enzymopathy Refsum disease Genetic disease Enzymatic activity Peroxisome Genetics Degenerative disease Peripheral nerve disease Mutation Localization Lipoidosis
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Summary:	Refsum disease is an autosomal-recessively inherited disorder characterized clinically by a tetrad of abnormalities: retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia and elevated protein levels in the cerebrospinal fluid (CSF) without an increase in the number of cells in the CSF. All patients exhibit accumulation of an unusual branched-chain fatty acid, phytanic acid (3,7,11,15-tetramethylhexadecanoic acid), in blood and tissues. Biochemically, the disease is caused by the deficiency of phytanoyl-CoA hydroxylase (PhyH), a peroxisomal protein catalyzing the first step in the alpha-oxidation of phytanic acid. We have purified PhyH from rat-liver peroxisomes and determined the N-terminal amino-acid sequence, as well as an additional internal amino-acid sequence obtained after Lys-C digestion of the purified protein. A search of the EST database with these partial amino-acid sequences led to the identification of the full-length human cDNA sequence encoding PhyH: the open reading frame encodes a 41.2-kD protein of 338 amino acids, which contains a cleavable peroxisomal targeting signal type 2 (PTS2). Sequence analysis of PHYH fibroblast cDNA from five patients with Refsum disease revealed distinct mutations, including a one-nucleotide deletion, a 111-nucleotide deletion and a point mutation. This analysis confirms our finding that Refsum disease is caused by a deficiency of PhyH.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Case Study-2 ObjectType-Feature-4 ObjectType-Report-1 ObjectType-Article-3
ISSN:	1061-4036 1546-1718
DOI:	10.1038/ng1097-190