Clinical and molecular genetic characteristics of patients with cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis (CTX) is a lipid storage disease caused by a deficiency of the mitochondrial enzyme 27-sterol hydroxylase (CYP 27), due to mutations in its gene. In this study we report on mutations in 58 patie nts with CTX out of 32 unrelated families. Eight of these were novel mutati ons, two of which were found together with two already known pathogenic mut ations, Twelve mutations found in this patient group have been described in the literature. In the patients from 31 families, mutations were found in both alleles, In the Literature, 28 mutations in 67 patients with CTX out o f 44 families have been described. Pooling our patient group and the patien ts from the literature together, 37 different mutations in 125 patients out of 74 families were obtained. Identical mutations have been found in famil ies from different ethnic backgrounds, In 41% of all the patients, CYP 27 g ene mutations are found in the region of exons 6-8, This region encodes for adrenodoxin and haem binding sites of the protein. Of these 125 patients, a genotype-phenotype analysis was done for 79 homozygous patients harbourin g 23 different mutations, out of 45 families. The patients with compound he terozygous mutations mere left out of the genotype-phenotype analysis. The genotype-phenotype analysis did not reveal any correlation.