A Novel Variant C.97C>T of the Growth Hormone Releasing Hormone Receptor Gene Causes Isolated Growth Hormone Deficiency Type Ib

Overview

Journal J Clin Res Pediatr Endocrinol

Specialties Endocrinology
Pediatrics

Date 2018 Mar 15

PMID 29537382

Citations 2

Authors

Assimina Galli-Tsinopoulou

Eleni P Kotanidou

Aggeliki N. Kleisarchaki

Rivka Kauli

Zvi Laron

Affiliations

Soon will be listed here.

Abstract

Congenital isolated growth hormone deficiency (IGHD) type 1b is an autosomal recessive genetic condition caused by mutations of growth hormone (GH)-1 or the growth hormone releasing hormone receptor () genes. Affected subjects present with symptoms of growth hormone deficiency (GHD) with low but detectable levels of growth hormone (GH), short stature and responsiveness to GH therapy. We describe a 13-month old girl with severe growth failure who showed a low GH response to two GH provocation tests and a modest increase of insulin-like growth factor-1 (IGF-1) to an IGF-1 generation test. Whole exome sequencing revealed a novel homozygous variant of the gene (c.97C>T), leading to a premature stop codon. Administration of recombinant human GH improved linear growth. This is the first report of a c.97C>T mutation of the gene.

Citing Articles

A GHRHR founder mutation causes isolated growth hormone deficiency type IV in a consanguineous Pakistani family.

Ahmad S, Ali M, Abbasi S, Abbas S, Ahmed I, Abbas S Front Endocrinol (Lausanne). 2023; 14:1066182.

PMID: 36960394 PMC: 10029353. DOI: 10.3389/fendo.2023.1066182.

An update on the diagnosis of growth hormone deficiency.

Gabreanu G Discoveries (Craiova). 2020; 6(1):e82.

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References

Wit J, Oostdijk W, Losekoot M, van Duyvenvoorde H, Ruivenkamp C, Kant S . MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature. Eur J Endocrinol. 2015; 174(4):R145-73. DOI: 10.1530/EJE-15-0937. View

Siklar Z, Berberoglu M, Legendre M, Amselem S, Evliyaoglu O, Hacihamdioglu B . Two siblings with isolated GH deficiency due to loss-of-function mutation in the GHRHR gene: successful treatment with growth hormone despite late admission and severe growth retardation. J Clin Res Pediatr Endocrinol. 2011; 2(4):164-7. PMC: 3005690. DOI: 10.4274/jcrpe.v2i4.164. View

Kale S, Budyal S, Kasaliwal R, Shivane V, Raghavan V, Lila A . A novel gross indel in the growth hormone releasing hormone receptor gene of Indian IGHD patients. Growth Horm IGF Res. 2014; 24(6):227-32. DOI: 10.1016/j.ghir.2014.07.003. View

Muraro A, Goncalves-Silva R, Moreira N, Ferreira M, Nunes-Freitas A, Abreu-Villaca Y . Effect of tobacco smoke exposure during pregnancy and preschool age on growth from birth to adolescence: a cohort study. BMC Pediatr. 2014; 14:99. PMC: 3989847. DOI: 10.1186/1471-2431-14-99. View

Laron Z . Deficiencies of growth hormone and somatomedins in man. Spec Top Endocrinol Metab. 1983; 5:149-99. View

Corazzini V, Salvatori R . Molecular and clinical aspects of GHRH receptor mutations. Endocr Dev. 2013; 24:106-17. DOI: 10.1159/000342575. View

Hawkes C, Grimberg A . Insulin-Like Growth Factor-I is a Marker for the Nutritional State. Pediatr Endocrinol Rev. 2016; 13(2):499-511. PMC: 5576178. View

Cogan J, Phillips 3rd J . GH1 gene deletions and IGHD type 1A. Pediatr Endocrinol Rev. 2008; 3 Suppl 3:480-8. View

Smuel K, Kauli R, Lilos P, Laron Z . Growth, development, puberty and adult height before and during treatment in children with congenital isolated growth hormone deficiency. Growth Horm IGF Res. 2015; 25(4):182-8. DOI: 10.1016/j.ghir.2015.05.001. View

10.

Baumann G . Genetic characterization of growth hormone deficiency and resistance: implications for treatment with recombinant growth hormone. Am J Pharmacogenomics. 2002; 2(2):93-111. DOI: 10.2165/00129785-200202020-00003. View

11.

Aguiar-Oliveira M, Souza A, Oliveira C, Campos V, Oliveira-Neto L, Salvatori R . MECHANISMS IN ENDOCRINOLOGY: The multiple facets of GHRH/GH/IGF-I axis: lessons from lifetime, untreated, isolated GH deficiency due to a GHRH receptor gene mutation. Eur J Endocrinol. 2017; 177(2):R85-R97. DOI: 10.1530/EJE-16-1047. View

12.

Inoue H, Kangawa N, Kinouchi A, Sakamoto Y, Kimura C, Horikawa R . Identification and functional analysis of novel human growth hormone-releasing hormone receptor (GHRHR) gene mutations in Japanese subjects with short stature. Clin Endocrinol (Oxf). 2010; 74(2):223-33. DOI: 10.1111/j.1365-2265.2010.03911.x. View

13.

Thomas M, Massa G, Craen M, de Zegher F, Bourguignon J, Heinrichs C . Prevalence and demographic features of childhood growth hormone deficiency in Belgium during the period 1986-2001. Eur J Endocrinol. 2004; 151(1):67-72. DOI: 10.1530/eje.0.1510067. View

14.

Faro A, Pereira-Gurgel V, Salvatori R, Campos V, Melo G, Oliveira F . Ocular findings in adult subjects with an inactivating mutation in GH releasing hormone receptor gene. Growth Horm IGF Res. 2017; 34:8-12. DOI: 10.1016/j.ghir.2017.04.002. View

15.

Laron Z, Kelijman M, Pertzelan A, KERET R, Shoffner J, Parks J . Human growth hormone gene deletion without antibody formation or growth arrest during treatment--a new disease entity?. Isr J Med Sci. 1985; 21(12):999-1006. View

16.

Shenassa E, Wen X, Braid S . Exposure to Tobacco Metabolites via Breast Milk and Infant Weight Gain: A Population-Based Study. J Hum Lact. 2015; 32(3):462-71. DOI: 10.1177/0890334415619154. View

17.

Inamdar A, Croucher R, Chokhandre M, Mashyakhy M, Marinho V . Maternal Smokeless Tobacco Use in Pregnancy and Adverse Health Outcomes in Newborns: A Systematic Review. Nicotine Tob Res. 2014; 17(9):1058-66. DOI: 10.1093/ntr/ntu255. View

18.

Maghnie M, Lindberg A, Koltowska-Haggstrom M, Ranke M . Magnetic resonance imaging of CNS in 15,043 children with GH deficiency in KIGS (Pfizer International Growth Database). Eur J Endocrinol. 2012; 168(2):211-7. DOI: 10.1530/EJE-12-0801. View

19.

Price S, Stanhope R, Garrett C, Preece M, Trembath R . The spectrum of Silver-Russell syndrome: a clinical and molecular genetic study and new diagnostic criteria. J Med Genet. 1999; 36(11):837-42. PMC: 1734267. View

20.

Marui S, Trarbach E, Boguszewski M, Franca M, Jorge A, Inoue H . GH-releasing hormone receptor gene: a novel splice-disrupting mutation and study of founder effects. Horm Res Paediatr. 2012; 78(3):165-72. DOI: 10.1159/000342760. View