Research Article
Year 2025,
Volume: 52 Issue: 1, 31 - 40, 14.03.2025
Abstract
References
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- 2.Health N.I.f. and C. Excellence, Human GrowthHormone (somatropin) for the Treatment of Growth Failure in Children: Review of NICE TechnologyAppraisal Guidance 42. 2010: National Institute forHealth and Clinical Excellence.
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- 7.Osorio, M.G.F., et al., Pituitary magnetic resonanceimaging and function in patients with growthhormone deficiency with and without mutations inGHRH-R, GH-1, or PROP-1 genes. The Journal ofClinical Endocrinology & Metabolism, 2002. 87(11):p.5076-84.
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- 17.Cogan J.D., et al., Heterogeneous growthhormone (GH) gene mutations in familial GHdeficiency. The Journal of Clinical Endocrinology &Metabolism, 1993. 76(5): p. 1224-8.
- 18.Alba M. and R. Salvatori, Naturally-occurringmissense mutations in the human growth hormone-releasing hormone receptor alter ligand binding.Journal of endocrinology, 2005. 186(3): p. 515-22.
- 19.Kılıç S. and İ. Esen, Büyüme Hormonu TedavisiAlan Çocukların Klinik Çzellikleri: Tek MerkezDeneyimi. Turkish Journal of Pediatric Disease,2021. 15(4): p. 287-93.
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- 21.Teran E., J. Chesner, and R. Rapaport, Growth and growth hormone: an overview. Growth Hormone &IGF Research, 2016. 28: p. 3-5.
- 22.Deal C., et al., Growth hormone treatment ofCanadian children: results from the GeNeSIS phaseIV prospective observational study. CanadianMedical Association Open Access Journal, 2018.6(3): p. E372-E83.
- 23.Alba P., S. Tsai, and N. Mitre, The severity ofgrowth hormone deficiency does not predict thepresence or absence of brain magnetic resonanceimaging abnormalities–a retrospective review.European endocrinology, 2020. 16(1): p. 60.
- 24. Özden A., Döneray H., & Orbak Z. (2022). BüyümeHormonu Tedavisi alan Çocukların Klinik Özelliklerive Tedaviye Yanıtlarının Değerlendirilmesi. DicleTıp Dergisi, 49(2), 352-60.
Clinical, Neuroradiological and Molecular Genetic Characteristics of 13 Patients Followed up for Growth Hormone Deficiency
Abstract
Objective: Growth hormone-releasing hormone (GHRH) and somatostatin are hypothalamic peptides that regulate pulsatile growth hormone (GH) secretion. GHRH binding to its receptor activates signaling, promoting cell proliferation, GH synthesis, and secretion. Mutations in the growth hormone-releasing hormone receptor (GHRHR) and growth hormone 1 (GH1) genes, which are involved in this pathway, occur as a rare cause of isolated growth hormone deficiency (IGHD). This study aimed to evaluate the clinical features, neuroradiological findings, and molecular genetic test results of 13 patients diagnosed with IGHD, as well as their responses to growth hormone treatment.
Methods: The study included 13 patients from six different consanguineous families who were being followed for isolated growth hormone deficiency. Using next-generation sequencing, biallelic disease-causing variants in the GHRHR and GH1 genes were identified in these patients. Clinical findings, family history, parental consanguinity, and neuroradiological images of the patients were retrospectively obtained from hospital records.
Results: Biallelic variants were identified in the GHRHR gene in nine patients and in the GH1 gene in four patients. The potential impact of these variants on protein structure was assessed using in silico prediction tools, including SIFT, MutationTaster, REVEL, and PolyPhen-2.
Conclusion: Screening for variants in the GH1 and GHRHR genes is recommended for patients with severe growth retardation, short stature. It is important to consider the possibility of multiple affected individuals presenting with similar phenotypes, particularly in regions with a high prevalence of consanguineous marriages. Therefore, comprehensive family screening should be conducted when appropriate.
Keywords
References
- 1.Birla S., et al., Identification of novel GHRHR andGH1 mutations in patients with isolated growthhormone deficiency. Growth Hormone & IGFResearch, 2016. 29: p. 50-6.
- 2.Health N.I.f. and C. Excellence, Human GrowthHormone (somatropin) for the Treatment of Growth Failure in Children: Review of NICE TechnologyAppraisal Guidance 42. 2010: National Institute forHealth and Clinical Excellence.
- 3.Mullis P.E., Genetics of isolated growth hormonedeficiency. Journal of clinical research in pediatricendocrinology, 2010. 2(2).
- 4.Vimpani G., et al., Prevalence of severe growthhormone deficiency. Br Med J, 1977. 2(6084): p.427-430.
- 5.Procter A.M., J.A. Phillips III, and D.N. Cooper, Themolecular genetics of growth hormone deficiency.Human genetics, 1998. 103: p. 255-72.
- 6.Alatzoglou, K.S. and M.T. Dattani, Phenotype-genotype correlations in congenital isolated growthhormone deficiency (IGHD). The Indian Journal ofPediatrics, 2012. 79: p. 99-106.
- 7.Osorio, M.G.F., et al., Pituitary magnetic resonanceimaging and function in patients with growthhormone deficiency with and without mutations inGHRH-R, GH-1, or PROP-1 genes. The Journal ofClinical Endocrinology & Metabolism, 2002. 87(11):p.5076-84.
- 8. Richards, S., et al., Standards and guidelines for theinterpretation of sequence variants: a jointconsensus recommendation of the American Collegeof Medical Genetics and Genomics and theAssociation for Molecular Pathology. Genetics inmedicine, 2015. 17(5): p. 405-23.
- 9.Mullis, P.E., Genetic control of growth. Europeanjournal of endocrinology, 2005. 152(1): p. 11-31.
- 10.Wagner J.K., et al., Prevalence of human GH-1gene alterations in patients with isolated growthhormone deficiency. Pediatric research, 1998.43(1): p. 105-10.
- 11.Mullis P., et al., Prevalence of human growthhormone-1 gene deletions among patients withisolated growth hormone deficiency from differentpopulations. Pediatric research, 1992. 31(5): p. 532-4.
- 12.Thomas P.Q., et al., Heterozygous HESX1mutations associated with isolated congenitalpituitary hypoplasia and septo-optic dysplasia.Human molecular genetics, 2001. 10(1): p. 39-45.
- 13.Woods K.S., et al., Over-and underdosage of SOX3is associated with infundibular hypoplasia andhypopituitarism. The American Journal of HumanGenetics, 2005. 76(5): p. 833-49.
- 14.Mullis, P.E., Genetics of growth hormonedeficiency. Endocrinology and Metabolism Clinics,2007. 36(1): p. 17-36.
- 15.De Graaff L.C., et al., Genetic screening of a Dutchpopulation with isolated GH deficiency (IGHD).Clinical endocrinology, 2009. 70(5): p. 742-50.
- 16.Alatzoglou K.S., et al., Expanding the spectrum ofmutations in GH1 and GHRHR: genetic screening ina large cohort of patients with congenital isolated growth hormone deficiency. The Journal of Clinical Endocrinology & Metabolism, 2009. 94(9): p. 3191-9.
- 17.Cogan J.D., et al., Heterogeneous growthhormone (GH) gene mutations in familial GHdeficiency. The Journal of Clinical Endocrinology &Metabolism, 1993. 76(5): p. 1224-8.
- 18.Alba M. and R. Salvatori, Naturally-occurringmissense mutations in the human growth hormone-releasing hormone receptor alter ligand binding.Journal of endocrinology, 2005. 186(3): p. 515-22.
- 19.Kılıç S. and İ. Esen, Büyüme Hormonu TedavisiAlan Çocukların Klinik Çzellikleri: Tek MerkezDeneyimi. Turkish Journal of Pediatric Disease,2021. 15(4): p. 287-93.
- 20.DARENDELİLER F.F., et al., Büyüme hormonueksikliği etiyolojisi, demografik veriler ve tedavisonuçlarının değerlendirilmesi: Türkiye verileri.KIGS (Pfizer Uluslar Arası Büyüme Veri Tabanı)analiz sonuçları. Çocuk Dergisi, 2004. 4(3): p. 141-8.
- 21.Teran E., J. Chesner, and R. Rapaport, Growth and growth hormone: an overview. Growth Hormone &IGF Research, 2016. 28: p. 3-5.
- 22.Deal C., et al., Growth hormone treatment ofCanadian children: results from the GeNeSIS phaseIV prospective observational study. CanadianMedical Association Open Access Journal, 2018.6(3): p. E372-E83.
- 23.Alba P., S. Tsai, and N. Mitre, The severity ofgrowth hormone deficiency does not predict thepresence or absence of brain magnetic resonanceimaging abnormalities–a retrospective review.European endocrinology, 2020. 16(1): p. 60.
- 24. Özden A., Döneray H., & Orbak Z. (2022). BüyümeHormonu Tedavisi alan Çocukların Klinik Özelliklerive Tedaviye Yanıtlarının Değerlendirilmesi. DicleTıp Dergisi, 49(2), 352-60.
There are 24 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration, Medical Education, Health Services and Systems (Other) |
| Journal Section | Original Articles |
| Authors | |
| Publication Date | March 14, 2025 |
| Submission Date | November 19, 2024 |
| Acceptance Date | January 27, 2025 |
| Published in Issue | Year 2025 Volume: 52 Issue: 1 |
