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Molecular study of human growth hormone gene cluster in three families with isolated growth hormone deficiency and similar phenotype

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Abstract

The growth hormone (GH) gene (hGH-N) cluster was analysed using polymerase chain reaction, Southern and polymorphism analysis in five patients (including two pairs of siblings) with extreme short stature and absence of GH secretion. Patients 1 and 2 (siblings) were homozygous for a large deletion removing four genes of the cluster: hGH-N, hCS-L, hCS-A and hGH-V Both siblings produced high anti-GH antibody levels in response to exogenous GH therapy, followed by growth arrest a few months after starting replacement therapy. In patient 3 we detected a heterozygous deletion which involved three genes of the cluster (hCS-A, hGH-V, hCS-B) and left an intact hGH-N gene. Direct sequencing of hGH-N specific amplified fragments excluded the presence of any point mutations in exons and splicing regions. In patients 4 and 5 (sisters) our study did not demonstrate any gene deletions. Analysis of polymorphic restriction patterns in this family demonstrated that both sisters inherited the same alleles from the father but different alleles from the mother, suggesting that the defect was not linked to the hGH-N gene. These results confirm the difficulty of clinical identification of subjects with hGH-N deletion and underline the importance of DNA analysis in patients with absence of GH secretion and extreme growth retardation.

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Abbreviations

GH :

growth hormone

GHRH :

growth hormone releasing hormone

IGHD :

isolated growth hormone deficiency

PCR :

polymerase chain reaction

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Authors and Affiliations

  1. Clinica Pediatrica I, Via Massarenti 11, I-40138, Bologna, Italy

    Emanuele Cacciari, Piero Pirazzoli, Stefano Gualandi, Stefano Zucchini, Antonio Balsamo & Alessandro Cicognani

  2. Central Laboratory, St. Orsola Hospital of Bologna, Italy

    Claudia Baroncini, Lilia Baldazzi, Barbara Trevisani & Maurizio Capelli

  3. Institute of Biochemistry, University of Ferrara, Italy

    Francesco Bernadi

Authors
  1. Emanuele Cacciari
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  2. Piero Pirazzoli
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  3. Stefano Gualandi
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  4. Stefano Zucchini
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  5. Antonio Balsamo
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  6. Alessandro Cicognani
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  7. Claudia Baroncini
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  8. Lilia Baldazzi
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  9. Barbara Trevisani
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  10. Maurizio Capelli
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  11. Francesco Bernadi
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Cacciari, E., Pirazzoli, P., Gualandi, S. et al. Molecular study of human growth hormone gene cluster in three families with isolated growth hormone deficiency and similar phenotype. Eur J Pediatr 153, 635–641 (1994). https://doi.org/10.1007/BF02190682

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  • DOI: https://doi.org/10.1007/BF02190682

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