title: Analysis of the chondroitin sulfate proteoglycan core protein (CSPGCP) gene in achondroplasia and pseudoachondroplasia.
abstract: Achondroplasia and pseudoachondroplasia are autosomal dominant skeletal dysplasias resulting in short-limbed dwarfism. Histologic and ultrastructural studies of the cartilage in pseudoachondroplasia and in homozygous achondroplasia have suggested a structural abnormality in chondroitin sulfate proteoglycan (CSPG), a major structural protein in the extra-cellular matrix. The gene encoding CSPG core protein (CSPGCP) is thus a logical "candidate gene" for analysis in these conditions. cDNA probes encoding CSPGCP were used to identify restriction fragment length polymorphisms (RFLPs) in DNA from a panel of control individuals. No gross alterations at the CSPGCP locus were noted in DNA from 37 individuals with achondroplasia and 5 individuals with pseudoachondroplasia. In addition, allelic frequencies of the RFLPs were not significantly different among controls and patients with either condition. In one three-generation family with achondroplasia, close linkage of the CSPGCP locus and the skeletal dysplasia was excluded using a Bgl II polymorphism. Similarly, in a three-generation family with pseudoachondroplasia, the CSPGCP gene was not tightly linked to the disease phenotype. These results indicate that mutations at the chondroitin sulfate proteoglycan core protein locus do not cause achondroplasia or pseudoachondroplasia in these families.
authors.affiliation: Department of Pediatrics, Johns Hopkins University, Baltimore, MD.
authors.forename: J E
authors.initials: JE
authors.lastname: Finkelstein
authors.forename: K
authors.initials: K
authors.lastname: Doege
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: R E
authors.initials: RE
authors.lastname: Pyeritz
authors.forename: J M
authors.initials: JM
authors.lastname: Graham
authors.forename: J B
authors.initials: JB
authors.lastname: Moeschler
authors.forename: R M
authors.initials: RM
authors.lastname: Pauli
authors.forename: J T
authors.initials: JT
authors.lastname: Hecht
authors.forename: C A
authors.initials: CA
authors.lastname: Francomano
mesh_terms: D000130:Achondroplasia / Q000235:genetics*; D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics*; D004247:DNA / Q000235:genetics; D016326:Extracellular Matrix Proteins; D005260:Female; D005819:Genetic Markers; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D037181:Lectins, C-Type; D008297:Male; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D011509:Proteoglycans
chemical_list: D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D005819:Genetic Markers; D006023:Glycoproteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D004247:DNA