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 CHILD syndrome, rare human skeletal dysplasias. These disorders also affect the skin and can cause cataracts and microphthalmia in surviving, affected heterozygous females. They have recently been shown to result from mutations in genes encoding enzymes involved in sequential steps in the conversion of lanosterol to cholesterol. This review will summarize clinical features of the disorders and describe recent biochemical and molecular investigations that have resulted in the elucidation of the involved genes and their metabolic pathway. Finally, speculations about possible mechanisms of pathogenesis will be provided.
Herman
G E
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Children's Research Institute and Department of Pediatrics, Ohio State University, 700 Children's Dr. Rm. W403, Columbus, OH 43205, USA. hermang@pediatrics.ohio-state.edu
D000015:Abnormalities, Multiple / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002784:Cholesterol / Q000032:analysis / Q000096:biosynthesis* / Q000097:blood; D002806:Chondrodysplasia Punctata / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D003873:Dermatitis, Exfoliative / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005804:Genes, Lethal; D006801:Humans; D007810:Lanosterol / Q000378:metabolism; D008297:Male; D051379:Mice; D008956:Models, Chemical; D009154:Mutation; D018901:Peroxisomal Disorders / Q000235:genetics; D012867:Skin / Q000378:metabolism; D013251:Steroid Isomerases; D013577:Syndrome; D014960:X Chromosome
D002352:Carrier Proteins; D007810:Lanosterol; D002784:Cholesterol; C490380:Ebp protein, mouse; D013251:Steroid Isomerases; C090445:EBP protein, human