title: Type IA isolated growth hormone deficiency (IGHD) consistent with compound heterozygous deletions of 6.7 and 7.6 Kb at the GH1 gene locus.
abstract: Isolated growth hormone deficiency (IGHD) may result from deletions/mutations in either GH1 or GHRHR genes. The objective of this study was to characterize the molecular defect in a girl presenting IGHD. The patient was born at 41 weeks of gestation from non-consanguineous parents. Clinical and biochemical evaluation included anthropometric measurements, evaluation of pituitary function, IGF-I and IGFBP-3 levels. Molecular characterization was performed by PCR amplification of GH1 gene and SmaI digestion of two homologous fragments flanking the gene, using genomic DNA from the patient and her parents as templates. At 1.8 years of age the patient presented severe growth retardation (height 61.2 cm, -7.4 SDS), truncal obesity, frontal bossing, doll face, and acromicria. MRI showed pituitary hypoplasia. Laboratory findings confirmed IGHD. GH1 gene could not be amplified in samples from the patient while her parents yielded one fragment of the expected size. SmaI digestion was consistent with the patient being compound heterozygous for 6.7 and 7.6 Kb deletions, while her parents appear to be heterozygous carriers for either the 6.7 or the 7.6 Kb deletions. We have characterized type IA IGHD caused by two different GH1 gene deletions, suggesting that this condition should be considered in severe IGHD, even in non-consanguineous families.
authors.affiliation: División Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.
authors.forename: Ana
authors.initials: A
authors.lastname: Keselman
authors.forename: Paula A
authors.initials: PA
authors.lastname: Scaglia
authors.forename: María Soledad
authors.initials: MS
authors.lastname: Rodríguez Prieto
authors.forename: María Gabriela
authors.initials: MG
authors.lastname: Ballerini
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Rodríguez
authors.forename: María Gabriela
authors.initials: MG
authors.lastname: Ropelato
authors.forename: Ignacio
authors.initials: I
authors.lastname: Bergadá
authors.forename: Héctor G
authors.initials: HG
authors.lastname: Jasper
authors.forename: Horacio M
authors.initials: HM
authors.lastname: Domené
mesh_terms: D001483:Base Sequence; D004393:Dwarfism, Pituitary / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D019382:Human Growth Hormone / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D019901:Locus Control Region / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D019382:Human Growth Hormone