X-linked dominant disorders of cholesterol biosynthesis in man and mouse

The X-linked dominant male-lethal mouse mutations tattered and bare patches are homologous to human X-linked dominant chondrodysplasia punctata and CH ILD syndrome, rare human skeletal dysplasias. These disorders also affect t he skin and can cause cataracts and microphthalmia in surviving, affected h eterozygous females. They have recently been shown to result from mutations in genes encoding enzymes involved in sequential steps in the conversion o f lanosterol to cholesterol. This review will summarize clinical features o f the disorders and describe recent biochemical and molecular investigation s that have resulted in the elucidation of the involved genes and their met abolic pathway. Finally, speculations about possible mechanisms of pathogen esis will be provided. (C) 2000 Elsevier Science B.V. All rights reserved.