2 NOVEL GENE-MUTATIONS (GLU174-]LYS, PHE383-]TYV) CAUSING THE HEPATICFORM OF CARNITINE PALMITOYLTRANSFERASE-II DEFICIENCY

Carnitine palmitoyltransferase II (CPT II) deficiency has two differen t clinical forms, one with ''hepatic'' and the other with ''muscular'' symptoms. We studied the molecular basis of the ''hepatic'' form in t wo Japanese siblings. Their CPT II activity in lymphoblasts was reduce d to 3% of the level observed in normal controls. cDNA analysis showed that the proband was a compound heterozygote, One allele carried a ne w mutation, G621-->A (Glu174-->Lys). The other carried three single-ba se substitutions; a new mutation, T1249-->A (Phe383-->Tyr), and two pr eviously reported polymorphisms. The brother had the same four substit utions. Neither of the two new mutations in this study was detected in the 60 alleles of 30 Japanese control subjects. Secondary structure p rediction analysis of the mutated CPT II protein was different from th at of the normal protein. We concluded that these mutations caused the ''hepatic'' form of CPT II deficiency in the probands.