title: Isolated growth hormone deficiency type 2: from gene to therapy.
abstract: Isolated growth hormone deficiency type-2 (IGHD-2), the autosomal-dominant form of GH deficiency, is mainly caused by specific splicing mutations in the human growth hormone (hGH) gene (GH-1). These mutations, occurring in and around exon 3, cause complete exon 3 skipping and produce a dominant-negative 17.5 kD GH isoform that reduces the accumulation and secretion of wild type-GH (wt-GH). At present, patients suffering from IGHD-2 are treated with daily injections of recombinant human GH (rhGH) in order to reach normal height. However, this type of replacement therapy, although effective in terms of growth, does not prevent toxic effects of the 17.5-kD mutant on the pituitary gland, which can eventually lead to other hormonal deficiencies. Considering a well-known correlation between the clinical severity observed in IGHD-2 patients and the increased expression of the 17.5-kD isoform, therapies that specifically target this isoform may be useful in patients with GH-1 splicing defects. This chapter focuses on molecular strategies that could represent future directions for IGHD-2 treatment.
authors.affiliation: University Children's Hospital, Pediatric Endocrinology, Diabetology and Metabolism, Inselspital, Bern, Switzerland. maria.miletta@dkf.unibe.ch
authors.forename: Maria Consolata
authors.initials: MC
authors.lastname: Miletta
authors.forename: Didier
authors.initials: D
authors.lastname: Lochmatter
authors.forename: Vibor
authors.initials: V
authors.lastname: Pektovic
authors.forename: Primus-E
authors.initials: PE
authors.lastname: Mullis
mesh_terms: D000818:Animals; D004393:Dwarfism, Pituitary / Q000235:genetics* / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism / Q000502:physiology; D020249:Hormone Replacement Therapy / Q000379:methods; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000502:physiology; D034622:RNA Interference / Q000502:physiology; D012326:RNA Splicing / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone