Genetic defects in GH synthesis and secretion

Bona, Gianni; Paracchini, R.; Giordano, Mara; Momigliano–Richiardi, Patricia

doi:10.1530/eje.0.151s003

Cited by 17 publications

(11 citation statements)

References 53 publications

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“…Growth hormone deficiency origins from a variety of disorders, e.g., genetic (reviewed in [213]) and acquired conditions resulting in various clinical symptoms with short stature in childhood and the adult GH deficiency syndrome (reviewed in [214]). A corner stone in the diagnosis of GHD is the GH response to a standardized stimulation test [109,110].…”

Section: Ghdmentioning

confidence: 99%

Physiology and pathophysiology of growth hormone-binding protein: Methodological and clinical aspects

Fisker

2006

Growth Hormone & IGF Research

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Section: Ghdmentioning

confidence: 99%

Physiology and pathophysiology of growth hormone-binding protein: Methodological and clinical aspects

Fisker

2006

Growth Hormone & IGF Research

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“…This genetically heterogeneous condition can be explained by mutations within key genes of the somatotroph axis, namely GH1 that encodes the growth hormone (GH), as well as GHSR and GHRHR, which encode the GH secretagogue receptor and the receptor of the GH releasing hormone (GHRH), respectively (Alatzoglou et al, 2009;Birla et al, 2016;Mullis, 2010;Pantel et al, 2006;Wajnrajch, Gertner, Harbison, Chua, & Leibel, 1996). Depending on studies, 5-30% of the cases for which a molecular cause has been found are familial (Alba et al, 2004;Bona, Paracchini, Giordano, & Momigliano-Richiardi, 2004;Lindsay, Feldkamp, Harris, Robertson, & Rallison, 1994). The GHRHR encodes a 423-amino-acid protein, which is a member of the secretin family of G-protein coupled receptors (GPCR).…”

Section: Introductionmentioning

confidence: 99%

Contribution of functionally assessed GHRHR mutations to idiopathic isolated growth hormone deficiency in patients without GH1 mutations

et al. 2019

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Isolated growth hormone deficiency (IGHD) is a rare condition mainly caused by mutations in GH1. The aim of this study was to assess the contribution of GHRHR mutations to IGHD in an unusually large group of patients. All GHRHR coding exons and flanking intronic regions were sequenced in 312 unrelated patients with nonsyndromic IGHD. Functional consequences of all newly identified missense variants were assessed in vitro (i.e., study of the expression of recombinant GHRHRs and their ability to activate the cyclic adenosine monophosphate (cAMP) signaling pathway). Genotype‐phenotype correlation analyses were performed according to the nature of the identified mutation. We identified 20 different disease‐causing GHRHR mutations (truncating and missense loss‐of‐function mutations), among which 15 are novel, in 24 unrelated patients. Of note, about half (13/24) of those patients represent sporadic cases. The clinical phenotype of patients with at least one missense GHRHR mutation was found to be indistinguishable from that of patients with bi‐allelic truncating mutations. This study, which unveils disease‐causing GHRHR mutations in 8% (24/312) of IGHD cases, identifies GHRHR as the second IGHD gene most frequently involved after GH1. The finding that 8% of IGHD cases without GH1 mutations are explained by GHRHR molecular defects (including missense mutations), together with the high proportion of sporadic cases among those patients, has important implications for genetic counseling.

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“…GHRH acts on GHRH receptor (GHRH-R) located in the plasma membrane of anterior pituitary somatotrophic cells and signals the somatroph to synthesise and secrete GH. Thus GH deficiency (GHD) can result from genetic defects in GH1 gene which codes for pituitary GH and GHRH-R gene coding for the GHRH receptor [1]. GHRH-R mutations are reported to be the cause of approximately 10% of isolated growth hormone deficiency with an autosomal recessive inheritance [2].…”

Section: Growth Hormone (Gh) Is Under Stimulatory and Inhibitory Contmentioning

confidence: 99%

Growth hormone releasing hormone receptor codon 72 mutation in a cohort of Sri Lankan patients with growth hormone deficiency

et al. 2016

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Introduction Growth hormone releasing hormone receptor (GHRH-R) codon 72 mutation is recognised as a common genetic cause of growth hormone deficiency (GHD) in the Indian subcontinent resulting in a characteristic lean phenotype. Genetic studies have not been previously carried out in Sri Lankans with GHD.Methods Patients with GHD presenting to a tertiary care referral centre were studied for GHRH-R codon 72 mutation by PCR amplification and sequencing. The phenotype of the cohort was described as the BMI SDS (Body mass index standard deviation score) based on the anthropometric data at the time of diagnosis.Results Among 91 patients from 88 families studied, eight (6 boys) carried the codon 72 mutation. The presence of this mutation was low among the Sinhalese ethnicity (3 out of 68) than among Tamil and Moor ethnicities. BMI SDS of <-2 was seen in 71% of mutation positive and 45.8% of mutation negative patients. ConclusionsPrevalence of GHRH-R codon 72 mutation in this group of GH deficient patients was 8.8%. The lean phenotype observed in 71% of the mutation positive patients was not a significant association when compared to a similar phenotype in 45.8% of the mutation negative patients. Growth hormone releasing hormone receptor codon 72 mutation in a cohort of Sri Lankan patients with growth hormone deficiency

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Genetic defects in GH synthesis and secretion

Cited by 17 publications

References 53 publications

Physiology and pathophysiology of growth hormone-binding protein: Methodological and clinical aspects

Physiology and pathophysiology of growth hormone-binding protein: Methodological and clinical aspects

Contribution of functionally assessed GHRHR mutations to idiopathic isolated growth hormone deficiency in patients without GH1 mutations

Growth hormone releasing hormone receptor codon 72 mutation in a cohort of Sri Lankan patients with growth hormone deficiency

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