Autosomal recessive form of isolated growth hormone deficiency is more frequent than the autosomal dominant form in a Brazilian cohort

Author(s)

Lido, Andria C. V. ^{[1, 2]} ; Franca, Marcela M. ^[2] ; Correa, Fernanda A. ^[2] ; Otto, Aline P. ^[2] ; Carvalho, Luciani R. ^[2] ; Quedas, Elisangela P. S. ^[1] ; Nishi, Mirian Y. ^[2] ; Mendonca, Berenice B. ^[2] ; Arnhold, Ivo J. P. ^[2] ; Jorge, Alexander A. L. ^[1]

Affiliation

^[1] Univ Sao Paulo, Hosp Clin, Fac Med, Unidade Endocrinol Genet, Lab Endocrinol Celular &, BR-01246903 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Hosp Clin, Fac Med, Unidade Endocrinol Desenvolvimento, Lab Hormonios, BR-05403900 Sao Paulo - Brazil

• Document type: Journal article
• Source: GROWTH HORMONE & IGF RESEARCH; v. 24, n. 5, p. 180-186, OCT 2014.
• Web of Science Citations: 1

Abstract

Background: In most studies, the autosomal dominant (type II) form of isolated growth hormone deficiency (IGHD) has been more frequent than the autosomal recessive (type I) form. Our aim was to assess defects in the GH1 in short Brazilian children with different GH secretion status. Subjects and methods: We selected 135 children with postnatal short stature and classified according to the highest GH peak at stimulation tests in: severe IGHD (peak GH <= 3.3 mu g/L, n = 38, all with normal pituitary magnetic resonance imaging); GH peak between 3.3 and 10 mu g/L (n = 76); and GH peak >10 mu g/L (n = 21). The entire coding region of GH1 was sequenced and complete GH1 deletions were assessed by Multiplex Ligation Dependent Probe Amplification and restriction enzyme digestion. Results: Patients with severe IGHD had a higher frequency of consanguinity, were shorter, had lower levels of IGF-1 and IGFBP-3, and despite treatment with lower GH doses had a greater growth response than patients with GH peak >= 3.3 mu g/L. Mutations were found only in patients with severe IGHD (GH peak <3.3 mu g/L). Eight patients had autosomal recessive IGHD: Seven patients were homozygous for GH1 deletions and one patient was compound heterozygous for a GH1 deletion and the novel c.171 + 5G>C point mutation in intron 2, predicted to abolish the donor splice site. Only one patient, who was heterozygous for the c.291 + 1G>T mutation located at the universal donor splice site of intron 3 and predicts exon 3 skipping, had an autosomal dominant form. Conclusion: Analysis of GH1 in a cohort of Brazilian patients revealed that the autosomal recessive form of IGHD was more common than the dominant one, and both were found only in severe IGHD. (C) 2014 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 13/03236-5 - New approaches and methodologies in molecular-genetic studies of growth and pubertal development disorders
• Grantee: Alexander Augusto de Lima Jorge
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 05/04726-0 - Molecular characterization of congenital endocrine diseases that affect growth and development
• Grantee: Ana Claudia Latronico Xavier
• Support Opportunities: Research Projects - Thematic Grants