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A case report and literature review of monoallelic mutation of GHR

  • Marie Mitani , Hirohito Shima , Takeshi Sato , Tomohiro Inoguchi , Tsutomu Kamimaki , Maki Fukami ORCID logo und Tomonobu Hasegawa EMAIL logo
Veröffentlicht/Copyright: 20. März 2019
Journal of Pediatric Endocrinology and Metabolism
Aus der Zeitschrift Journal of Pediatric Endocrinology and Metabolism Band 32 Heft 4

Abstract

Background

Monoallelic mutations of GHR have been described in idiopathic short stature (ISS), although the significance of these remain unclear. We report a case of ISS with novel monoallelic S219L mutation of GHR and discuss the possible significance of monoallelic GHR mutation in ISS.

Case presentation

The proband, a 13.9-year-old Japanese boy, had severe short stature (−3.8 standard deviation [SD]). Serum insulin-like growth factor (IGF)-I level and growth hormone (GH) secretion was normal. His parents were nonconsanguineous and had normal stature. Genetic analyses revealed a novel monoallelic missense variation in exon 7 of GHR (S219L). The proband’s mother had the same variation. S219L might be the novel mutation judging from there being no registration of it as a single-nucleotide polymorphism (SNP) in any database, evolutional conservation of Ser219, in silico analyses, and computational molecular visualization analysis. Furthermore, a review of the literature showed that the median height of missense mutation carriers of GHR was relatively low.

Conclusions

We propose the possibility that monoallelic mutation of GHR increases the susceptibility to short stature.

Keywords: GH insensitivity; GH receptor; idiopathic short stature
Corresponding author: Tomonobu Hasegawa, MD, PhD, Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan, Phone: +81-3-3353-1211, Fax: +81-3-5379-1978

Acknowledgments

This study was partly supported by a research grant from Japan Chemical Research (JCR) Pharmaceuticals.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This study was supported in part by a research grant from JCR pharmaceuticals.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interest: The funding organization played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/jpem-2018-0365).

Received: 2018-08-18
Accepted: 2019-01-29
Published Online: 2019-03-20
Published in Print: 2019-04-24

©2019 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/jpem-2018-0365
Schlagwörter für diesen Artikel
GH insensitivity; GH receptor; idiopathic short stature

Artikel in diesem Heft

  1. Frontmatter
  2. Review
  3. The importance of anthropological methods in the diagnosis of rare diseases
  4. Original Articles
  5. PON1 arylesterase activity, HDL functionality and their correlation in malnourished children
  6. Prevalence of dyslipidemia and factors affecting dyslipidemia in young adults with type 1 diabetes: evaluation of statin prescribing
  7. Myocardial dysfunction in relation to serum thiamine levels in children with diabetic ketoacidosis
  8. Evaluation of long-term follow-up and methimazole therapy outcomes of pediatric Graves’ disease: a single-center experience
  9. Endocrine consequences of neuroblastoma treatment in children: 20 years’ experience of a single center
  10. Analysis of diabetes-associated autoantibodies in children and adolescents with autoimmune thyroid diseases
  11. Adrenal function of extremely premature infants in the first 5 days after birth
  12. Atypical presentation of Leydig cell tumour in three prepubertal patients: diagnosis, treatment and outcomes
  13. The diagnosis of cystinosis in patients reveals new CTNS gene mutations in the Chinese population
  14. Comparing the validity of continuous metabolic syndrome risk scores for predicting pediatric metabolic syndrome: the CASPIAN-V study
  15. Primary pigmented nodular adrenocortical disease (PPNAD): single centre experience
  16. Short Communication
  17. Classical galactosemia patients can achieve high IQ scores
  18. Case Reports
  19. Idiopathic gonadotropin-independent precocious puberty – is regular surveillance required?
  20. MYT1L mutation in a patient causes intellectual disability and early onset of obesity: a case report and review of the literature
  21. A case report and literature review of monoallelic mutation of GHR
  22. Pitfalls in the diagnosis of insulin autoimmune syndrome (Hirata’s disease) in a hypoglycemic child: a case report and review of the literature
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