Recessive Isolated Growth Hormone Deficiency and Mutations in the Ghrelin Receptor

Pantel, Jacques; Legendre, M.; Nivot, S.; Morisset-Lopez, Séverine; Vié-Luton, Marie-Pierre; Bouc, Yves Le; Epelbaum, Jacques; Amselem, Serge

doi:10.1210/jc.2009-1327

Cited by 86 publications

(67 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast to the Ala204Glu mutation which has been implicated in short stature with dominant transmission; recessive GHS-R mutations have also been reported (Pantel et al, 2009). The proband was born to unrelated parents of normal phenotype, presented with episodes of abdominal pain, vomiting, hypoglycemia, and ketosis and required glucose infusions.…”

Section: Ghs-r Mutations In Patientsmentioning

confidence: 97%

“…GHS-R sequencing revealed that the patient was compound heterozygous for two new defects: a mutation predicting a premature stop codon (Trp2X) inherited from his unaffected father, therefore strongly arguing against haploinsufficiency as a disease mechanism, and a missense mutation (Arg237Trp), inherited from his healthy mother (Pantel et al, 2009).…”

Section: Ghs-r Mutations In Patientsmentioning

confidence: 99%

See 1 more Smart Citation

Ghrelin in obesity and endocrine diseases

Scerif

Goldstone

Korbonits

2011

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

Section: Ghs-r Mutations In Patientsmentioning

confidence: 97%

Section: Ghs-r Mutations In Patientsmentioning

confidence: 99%

Ghrelin in obesity and endocrine diseases

Scerif

Goldstone

Korbonits

2011

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

“…Later, this group also reported a patient with isolated GH deficiency due to compound heterozygous GHSR mutations (10). Similarly, a significantly higher occurrence of four novel heterozygous GHSR variants was observed in 127 Japanese patients with either GH deficiency or short stature compared with controls (4.72 vs 0.53%) (11).…”

Section: Introductionmentioning

confidence: 91%

GH secretagogue receptor gene polymorphisms are associated with stature throughout childhood

Riedl

Hughes²,

Harris³

et al. 2012

European Journal of Endocrinology

View full text Add to dashboard Cite

Context: Ghrelin plays a major role in GH physiology and energy metabolism. Polymorphisms of its receptor (GH secretagogue receptor (GHSR)) may influence childhood growth and weight regulation. Objective: To correlate GHSR polymorphisms with auxological parameters throughout childhood in a healthy cohort. Study design: Longitudinal retrospective population-based genetic association study. Subjects and methods: GHSR genotypes were evaluated in 1362 children and compared with height/length, weight, and body mass index (BMI) data across an observation span of 10 years (0, 1, 3, 5, 8, and 10 years). Five different GHSR SNPs (rs2922126, rs2981464, rs482204, rs562416, and rs572169), minor allele frequency O0.1, were genotyped. Identification of potential genetic associations with height, weight, and BMI, using additive and dominant/recessive models, was optimized by comparing allele or genotype frequencies between the tallest and the shortest 27% of subjects for each auxological variable. Significance of association was evaluated by c 2 test. Results: The rs482204 TT genotype, vs TC/CC, was associated with greater stature across the entire observation period (P!0.05). Similarly, the rs562416 TT genotype, vs TG/GG, correlated positively with tall stature at 3, 8, and 10 years. Other SNPs and genotypes showed no association with height at any age. No association was found between any tested SNPs and weight or BMI. Conclusions: Longitudinal investigation between birth and 10 years in a population-based cohort revealed a significant association of the rs482204 and rs562416 GHSR polymorphisms on height, whereas no association between GHSR polymorphisms and weight or BMI was ascertainable.

show abstract

“…We used two naturally occurring GHSR mutations that lead to either partial or complete lack of basal ligand-independent activity: A204E and F279L (supplemental Fig. S2) (36,37). Such mutations can be termed silencing mutations, inverse agonistic mutations, or constitutively inactivating mutations.…”

Section: Coexpression Of Mc3r and Ghsr In Hypothalamic Neurons-mentioning

confidence: 99%

Mutually Opposite Signal Modulation by Hypothalamic Heterodimerization of Ghrelin and Melanocortin-3 Receptors

Rediger

Piechowski

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: The melanocortin-3 (MC3R) and ghrelin (GHSR) receptors are important key components in hypothalamic weight regulation. Results: MC3R and GHSR di/oligomerize and have an opposite impact on each other's function. Conclusion:The high basal activity of GHSR is a determinant of heterodimer function, and MC3R may constrain GHSR function. Significance: Receptor di/oligomerization and its functional relevance contribute to the complex network of hypothalamic weight regulation.

show abstract

Recessive Isolated Growth Hormone Deficiency and Mutations in the Ghrelin Receptor

Abstract: These data, which describe the first case of recessive partial isolated GH deficiency due to GHSR mutations and emphasize the physiological importance of the GHSR in somatic growth, are discussed in light of the dominantly expressed p.A204E mutation.

Cited by 86 publications

References 30 publications

Ghrelin in obesity and endocrine diseases

Ghrelin in obesity and endocrine diseases

GH secretagogue receptor gene polymorphisms are associated with stature throughout childhood

Mutually Opposite Signal Modulation by Hypothalamic Heterodimerization of Ghrelin and Melanocortin-3 Receptors

Contact Info

Product

Resources

About