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Heterozygous GHR gene mutation in a child with idiopathic short stature

  • Sara Pagani , Vibor Petkovic , Beatrice Messini , Cristina Meazza , Elena Bozzola , Primus-E. Mullis and Mauro Bozzola EMAIL logo
Published/Copyright: October 23, 2013
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 27 Issue 3-4

Abstract

Several monogenic defects have been reported to be associated with idiopathic short stature. Focusing on growth hormone receptor (GHR)-gene alterations, the heterozygosity of the same gene defect may be associated with a range of growth deficits. We found a heterozygous mutation (V144I) within exon 6 of the GHR gene in a patient with a low level of insulin-like growth factor I (IGF-I), normal level of GH, and severe short stature. Despite the lack of statistical difference, an overall tendency for reduced wt-GH-induction of GHR activation and Jak/Stat signalling in cells transiently expressing GHR-V144I alone or co-expressing wt-GHR compared to cells expressing only wt-GHR was found when GH doses were increased. Our results suggest that, although GHR sequence variants are responsible for some functional alterations commonly observed in children with idiopathic short stature, these changes may not explain all the height deficits observed in these subjects.

Keywords: GH; GHR gene mutation; idiopathic short stature; IGF-I
Corresponding author: Mauro Bozzola, MD, Internal Medicine and Therapeutics Department, University of Pavia, Fondazione IRCCS Policlinico San Matteo, Piazzale Golgi, 2, 27100 Pavia, Italy, Phone: +390382501270, Fax: +390382502876, E-mail:
aThese authors contributed equally to the writing of the manuscript.

Acknowledgments

The authors are grateful to Laurene Kelly for her English language revision of the paper.

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Received: 2013-9-4
Accepted: 2013-9-11
Published Online: 2013-10-23
Published in Print: 2014-03-01

©2014 by Walter de Gruyter Berlin Boston

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  38. 10.1515/jpem-2014-0999
https://doi.org/10.1515/jpem-2013-0359
Keywords for this article
GH; GHR gene mutation; idiopathic short stature; IGF-I

Articles in the same Issue

  1. Masthead
  2. Masthead
  3. Images in pediatric endocrinology
  4. Leprechaunism (Donohue syndrome): report of a case in a newborn
  5. Original articles
  6. Children and adolescents with type 1 diabetes in Germany are more overweight than healthy controls: results comparing DPV database and CrescNet database
  7. Age of onset of pubertal maturation of Thai boys
  8. Plasma leptin and adiponectin concentrations correlate with cardiometabolic risk and systemic inflammation in healthy, non-obese children
  9. Early differentiation between good and poor response to growth hormone therapy in short children born small for gestational age (SGA) to improve the outcome of poor responders
  10. Children and adolescents with type 1 diabetes mellitus have a sixfold greater risk for prolonged QTc interval
  11. Effect of micronutrient supplementation on height velocity of underprivileged girls in comparison with un-supplemented healthy controls
  12. Insulin resistance in young adults born small for gestational age (SGA)
  13. The effect of childhood obesity on cardiac functions
  14. Adiponectin serum concentrations in newborn at delivery appear to be of fetal origin
  15. Thalassaemic Osteopathy: a cross-sectional preliminary study from Sri Lanka
  16. Health-related quality of life in Turner syndrome and the influence of key features
  17. Clinical analysis on 33 patients with hypothalamic syndrome in Chinese children
  18. The relationship between thyroid dose and diagnosis of primary hypothyroidism in pediatric brain tumor patients receiving craniospinal irradiation
  19. Molecular characterization of Chilean patients with a clinical diagnosis of Noonan syndrome
  20. Expensive therapies in children: benefit versus cost of combined treatment of recombinant human growth hormone and gonadotropin-releasing hormone analogue in girls with poor height potential
  21. The absence of mutations in homeobox candidate genes HOXA3, HOXB3, HOXD3 and PITX2 in familial and sporadic thyroid hemiagenesis
  22. A truncating DUOX2 mutation (R434X) causes severe congenital hypothyroidism
  23. Heterozygous GHR gene mutation in a child with idiopathic short stature
  24. A novel compound mutation of CYP27B1 in a Chinese family with vitamin D-dependent rickets type 1A
  25. A de novo mutation of DAX1 in a boy with congenital adrenal hypoplasia without hypogonadotropic hypogonadism
  26. Patient reports
  27. Hypercalcemia and osteolytic lesions as presenting symptoms of acute lymphoblastic leukemia in childhood. The use of zoledronic acid and review of the literature
  28. Preterm ovarian hyperstimulation syndrome presented with vaginal bleeding: a case report
  29. Pituitary stalk lesion in a 13-year-old female
  30. Radiologic manifestation of a BCS1L-mutated patient
  31. Permanent neonatal diabetes mellitus caused by a novel mutation in the KCNJ11 gene
  32. NKX2-1 mutations in brain-lung-thyroid syndrome: a case series of four patients
  33. A teenage boy with hypocalcemia after radioablation for Graves’ disease
  34. Short communication
  35. A common thyroid peroxidase gene mutation (G319R) in Turkish patients with congenital hypothyroidism could be due to a founder effect
  36. Letter to the Editor
  37. Endometriosis and migraine: what is there behind the scenes?
  38. 10.1515/jpem-2014-0999
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