title: Genetic and biochemical heterogeneity in patients with the rhizomelic form of chondrodysplasia punctata--a complementation study.
abstract: The genetic relationship between 10 patients with clinical manifestations of rhizomelic chondrodysplasia punctata (RCDP) was studied by complementation analysis after somatic cell fusion. Biochemically, 9 out of the 10 patients were characterized by a partial deficiency of acyl-CoA: dihydroxyacetone phosphate acyltransferase (DHAP-AT) and an impairment of plasmalogen biosynthesis, phytanate catabolism and the maturation of peroxisomal 3-oxoacyl-CoA thiolase; 3-oxoacyl-CoA thiolase was strongly reduced in the peroxisomes of these patients. Fusion of fibroblasts from these 9 patients with Zellweger fibroblasts resulted in complementation as indicated by the restoration of DHAP-AT activity, plasmalogen biosynthesis, and punctate fluorescence after staining with a monoclonal antibody to peroxisomal thiolase. No complementation was observed after fusion of different combinations of the 9 RCDP cell lines, suggesting that they belong to a single complementation group. The tenth patient was characterized biochemically by a deficiency of DHAP-AT and an impairment of plasmalogen biosynthesis. However, maturation and localization of peroxisomal thiolase were normal. Fusion of fibroblasts from this patient with fibroblasts from the other 9 patients resulted in complementation as indicated by the restoration of plasmalogen biosynthesis. We conclude that mutations in at least two different genes can lead to the clinical phenotype of RCDP.
authors.affiliation: E.C. Slater Institute for Biochemical Research, University of Amsterdam, The Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: Heikoop
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanders
authors.forename: A
authors.initials: A
authors.lastname: Strijland
authors.forename: R
authors.initials: R
authors.lastname: Purvis
authors.forename: R B
authors.initials: RB
authors.lastname: Schutgens
authors.forename: J M
authors.initials: JM
authors.lastname: Tager
mesh_terms: D000102:Acetyl-CoA C-Acyltransferase / Q000378:metabolism; D000217:Acyltransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D019883:Alkyl and Aryl Transferases; D002459:Cell Fusion; D002460:Cell Line; D002806:Chondrodysplasia Punctata / Q000235:genetics* / Q000378:metabolism; D005816:Genetic Complementation Test; D006801:Humans; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D010831:Phytanic Acid / Q000378:metabolism; D010955:Plasmalogens / Q000096:biosynthesis; D014166:Transferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D010955:Plasmalogens; D010831:Phytanic Acid; D014166:Transferases; D000217:Acyltransferases; D000102:Acetyl-CoA C-Acyltransferase; C020051:glycerone-phosphate O-acyltransferase; D019883:Alkyl and Aryl Transferases; C019654:alkylglycerone-phosphate synthase