NOVEL HOMOZYGOUS AND COMPOUND HETEROZYGOUS MUTATIONS OF STEROL 27-HYDROXYLASE GENE (CYP27) CAUSE CEREBROTENDINOUS XANTHOMATOSIS IN 3 JAPANESE PATIENTS FROM 2 UNRELATED FAMILIES

The autosomal recessively inherited cholesterol metabolic disease, cer ebrotendinous xanthomatosis (CTX), is caused by mutations in the stero l 27-hydroxylase gene. Three Japanese CTX patients from two unrelated families were studied genetically. By DNA sequence analysis a novel mu tation of A for G substitution at amino acid position 372 (CGG (372)Ar g to CAG (372)Gln) was identified in one of the CTX families. The muta tion was also found in two patients from the other family, with a comp ound heterozygous pattern of A for G substitution at amino acid positi on 441 (CGG (441)Arg to CAG (441)Gln). The latter mutation was the sam e as previously reported by our group (J. Lipid Res. 1994. 35: 1031-10 39). As the two mutations changed the restriction enzyme sites, rapid screening methods were developed for the detection of the carriers. Tr ansfection of the two mutant cDNAs into COS cells resulted in markedly reduced sterol 27-hydroxylase activity. These results indicate that t he two mutations are responsible for the deficiency of the sterol 27-h ydroxylase activity in these patients. The features of mutations ident ified till now in Japanese CTX patients are also reviewed.