Novel compound heterozygous mutations of the growth hormone-releasing hormone receptor gene in a case of isolated growth hormone deficiency

Akiko Soneda, Masanori Adachi, Koji Muroya, Yumi Asakura, Masaki Takagi, Tomonobu Hasegawa, Hiroshi Inoue, Mitsuo Itakura

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Objective: To elucidate the pathogenesis of isolated growth hormone (GH) deficiency in a Japanese girl without consanguinity. Design: A 2-year-old girl of height 77.2. cm (-. 3.0 SD for Japanese girls) was found to have an insulin-like growth factor (IGF)-1 level of 7. ng/mL and IGF binding protein-3 (IGFBP-3) level of 0.41. μg/mL. GH responded modestly to a series of pharmacological stimulants, increasing to 2.81. ng/mL with insulin-induced hypoglycemia, 3.78. ng/mL with arginine, and 3.93 with GH-releasing hormone (GHRH). Following direct sequencing of the GHRH receptor (. GHRHR) gene, evaluation by the luciferase reporter assay, immunofluorescence study, and in vitro splicing assay with minigene constructs was conducted. Results: Novel compound heterozygous GHRHR gene mutations were identified in the patient. A p.G136V substitution elicited no luciferase activity increment in response to GHRH stimulation, with normal membranous expression. Splicing assay demonstrated that the IVS2. +. 3a. >. g mutation would lead to aberrant splicing. Conclusions: A case of isolated GH deficiency due to novel GHRHR gene mutations was identified.

Original languageEnglish
Pages (from-to)89-97
Number of pages9
JournalGrowth Hormone and IGF Research
Volume23
Issue number4
DOIs
Publication statusPublished - 2013 Aug 1

Keywords

  • Growth hormone-releasing hormone receptor
  • Isolated growth hormone deficiency
  • Pituitary hypoplasia
  • Short stature
  • Splice donor site

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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