title: Isolated growth hormone deficiency type IA associated with a 45-kilobase gene deletion within the human growth hormone gene cluster in an Italian family.
abstract: An Italian family with three children presenting with isolated growth hormone (GH) deficiency type IA is described. Restriction endonuclease analysis revealed that the cause of hGH deficiency was a 45-kb gene deletion within the hGH-chorionic somatomammotropin (CS) gene cluster, encompassing the GH-1, CS-L, CS-A, and GH-2 genes. DNA sequence analysis and polymerase chain reaction amplification between two sequences located on each side of the deletion breakpoint accurately identified the deletion breakpoints and indicated that the regulatory sequences located upstream from the TATA box of the mutant CS-B belong to the GH-2 gene. Two of the affected children developed high-titer anti-hGH antibodies after recombinant hGH treatment with secondary growth arrest, whereas the third one maintained normal growth in the presence of very low-titer antibodies. This is the first report of a large deletional mutation within the hGH-CS gene cluster accompanied by phenotypic heterogeneity in terms of growth response and antibody formation in the different patients.
authors.affiliation: Department of Pediatrics, University of Parma, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Ghizzoni
authors.forename: P
authors.initials: P
authors.lastname: Duquesnoy
authors.forename: T
authors.initials: T
authors.lastname: Torresani
authors.forename: A
authors.initials: A
authors.lastname: Vottero
authors.forename: M
authors.initials: M
authors.lastname: Goossens
authors.forename: S
authors.initials: S
authors.lastname: Bernasconi
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D005260:Female; D017353:Gene Deletion; D013006:Growth Hormone / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D007223:Infant; D007558:Italy; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family; D010375:Pedigree; D010928:Placental Lactogen / Q000235:genetics; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping
chemical_list: D013006:Growth Hormone; D010928:Placental Lactogen