title: A broad spectrum of genomic changes in latinamerican patients with EXT1/EXT2-CDG.
abstract: Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). In contrast, solitary osteochondroma (SO) is a non-hereditary condition. EXT1 and EXT2, are tumor suppressor genes that encode glycosyltransferases involved in heparan sulfate elongation. We present the clinical and molecular analysis of 33 unrelated Latin American patients (27 MO and 6 SO). Sixty-three percent of all MO cases presented severe phenotype and two malignant transformations to chondrosarcoma (7%). We found the mutant allele in 78% of MO patients. Ten mutations were novel. The disease-causing mutations remained unknown in 22% of the MO patients and in all SO patients. No second mutational hit was detected in the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation. Neither EXT1 nor EXT2 protein could be detected in this sample. This is the first Latin American research program on EXT1/EXT2-CDG.
authors.affiliation: Centro de Estudio de las Metabolopatías Congénitas (CEMECO), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Hospital de Niños de la Santísima Trinidad, Córdoba, Argentina.
authors.forename: M A
authors.initials: MA
authors.lastname: Delgado
authors.affiliation: Centro de Estudio de las Metabolopatías Congénitas (CEMECO), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Hospital de Niños de la Santísima Trinidad, Córdoba, Argentina.
authors.forename: G
authors.initials: G
authors.lastname: Martinez-Domenech
authors.affiliation: Universitat de Barcelona, IBUB, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Departament de Genética, Facultat de Biología, Barcelona, España.
authors.forename: P
authors.initials: P
authors.lastname: Sarrión
authors.affiliation: Universitat de Barcelona, IBUB, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Departament de Genética, Facultat de Biología, Barcelona, España.
authors.forename: R
authors.initials: R
authors.lastname: Urreizti
authors.affiliation: Servicio de Traumatología, Hospital de Niños de la Santísima Trinidad, Córdoba, Argentina.
authors.forename: L
authors.initials: L
authors.lastname: Zecchini
authors.affiliation: Servicio de Bioimágenes, Hospital de Niños de la Santísima Trinidad, Córdoba, Argentina.
authors.forename: H H
authors.initials: HH
authors.lastname: Robledo
authors.affiliation: IIda Cátedra de Ortopedia y Traumatología, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Argentina.
authors.forename: F
authors.initials: F
authors.lastname: Segura
authors.affiliation: Centro de Estudio de las Metabolopatías Congénitas (CEMECO), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Hospital de Niños de la Santísima Trinidad, Córdoba, Argentina.
authors.forename: R Dodelson
authors.initials: RD
authors.lastname: de Kremer
authors.affiliation: Universitat de Barcelona, IBUB, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Departament de Genética, Facultat de Biología, Barcelona, España.
authors.forename: S
authors.initials: S
authors.lastname: Balcells
authors.affiliation: Universitat de Barcelona, IBUB, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Departament de Genética, Facultat de Biología, Barcelona, España.
authors.forename: D
authors.initials: D
authors.lastname: Grinberg
authors.affiliation: 1] Centro de Estudio de las Metabolopatías Congénitas (CEMECO), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Hospital de Niños de la Santísima Trinidad, Córdoba, Argentina [2] Cátedra de Farmacología, Facultad de Medicina, Universidad Católica de Córdoba, Argentina [3] Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.
authors.forename: C G
authors.initials: CG
authors.lastname: Asteggiano
mesh_terms: D016022:Case-Control Studies; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005097:Exostoses, Multiple Hereditary / Q000235:genetics*; D005260:Female; D023281:Genomics / Q000379:methods*; D006801:Humans; D007843:Latin America / Q000208:ethnology; D019656:Loss of Heterozygosity; D008297:Male; D009154:Mutation / Q000235:genetics*; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014481:United States; D000099065:Exostosin 2; D000099058:Exostosin 1
chemical_list: D017351:N-Acetylglucosaminyltransferases; D000099058:Exostosin 1; D000099065:Exostosin 2