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Molecular basis of long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency: Identification of two new mutations
Author(s) -
IJlst L.,
Oostheim W.,
Ruitter J. P. N.,
Wanders R. J. A.
Publication year - 1997
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1023/a:1005310903004
Subject(s) - biochemistry , medicine , university hospital , library science , chemistry , family medicine , computer science
Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) is catalysed by the mitochondrial trifunctional protein (MTP), which also contains enoyl-CoA hydratase and 3-ketothiolase activities (Carpenter et al 1992; Uchida et al 1992). The cDNAs encoding the a and β subunits were cloned by Kamijo et al (1994a). Many patients have been described with a defect in this enzyme complex and it appears that in most patients there is an isolated deficiency of the dehydrogenase activity of the MTP. We and others have reported a G1528C mutation in the gene coding for the α subunit of MTP, changing the codon for glutamate (510) into glutamine (IJ1st et al 1994; Sims et al 1995). In a series of 34 LCHAD-deficient patients the G1528C mutation was found to be very frequent (87%), which corresponds to the situation observed in MCAD deficiency with the frequent G985A mutation. The G1528C mutation is directly responsible for the loss of dehydrogenase activity without changing the structure of the enzyme complex (IJ1st et al 1996). In a group of 46 LCHAD-deficient patients as studied enzymatically in our laboratory, we found 12 to be compound heterozygous for the common mutation. Here we describe two new mutations found in this compound heterozygous group.