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dc.contributor.author
Duckett, Katie
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Williamson, Alice
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Kincaid, John W. R.
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Rainbow, Kara
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Corbin, Laura J.
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Martin, Hilary C.
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Eberhardt, Ruth Y.
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Huang, Qin Qin
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Hurles, Matthew E.
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He, Wen
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Brauner, Raja
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Delaney, Angela
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Dunkel, Leo
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Grinspon, Romina
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Hall, Janet E
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Hirschhorn, Joel N.
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Howard, Sasha R.
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Latronico, Ana C.
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Jorge, Alexander A. L.
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McElreavey, Ken
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Mericq, Verónica
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Merino, Paulina M.
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Palmert, Mark R.
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Plummer, Lacey
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Rey, Rodolfo Alberto
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Rezende, Raíssa C.
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Seminara, Stephanie B.
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Salnikov, Kathryn
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Banerjee, Indraneel
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Lam, Brian Y. H.
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Perry, John R. B.
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Timpson, Nicholas J.
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Clayton, Peter
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Chan, Yee Ming
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Ong, Ken K.
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O’Rahilly, Stephen
dc.date.available
2024-03-11T15:44:32Z
dc.date.issued
2023-06
dc.identifier.citation
Duckett, Katie; Williamson, Alice; Kincaid, John W. R.; Rainbow, Kara; Corbin, Laura J.; et al.; Prevalence of Deleterious Variants in MC3R in Patients With Constitutional Delay of Growth and Puberty; Endocrine Society; Journal of Clinical Endocrinology and Metabolism; 108; 12; 6-2023; e1580-e1587
dc.identifier.issn
0021-972X
dc.identifier.uri
http://hdl.handle.net/11336/230068
dc.description.abstract
Context The melanocortin 3 receptor (MC3R) has recently emerged as a critical regulator of pubertal timing, linear growth, and the acquisition of lean mass in humans and mice. In population-based studies, heterozygous carriers of deleterious variants in MC3R report a later onset of puberty than noncarriers. However, the frequency of such variants in patients who present with clinical disorders of pubertal development is currently unknown. Objective This work aimed to determine whether deleterious MC3R variants are more frequently found in patients clinically presenting with constitutional delay of growth and puberty (CDGP) or normosmic idiopathic hypogonadotropic hypogonadism (nIHH). Methods We examined the sequence of MC3R in 362 adolescents with a clinical diagnosis of CDGP and 657 patients with nIHH, experimentally characterized the signaling properties of all nonsynonymous variants found and compared their frequency to that in 5774 controls from a population-based cohort. Additionally, we established the relative frequency of predicted deleterious variants in individuals with self-reported delayed vs normally timed menarche/voice-breaking in the UK Biobank cohort. Results MC3R loss-of-function variants were infrequent but overrepresented in patients with CDGP (8/362 [2.2%]; OR = 4.17; P = .001). There was no strong evidence of overrepresentation in patients with nIHH (4/657 [0.6%]; OR = 1.15; P = .779). In 246 328 women from the UK Biobank, predicted deleterious variants were more frequently found in those self-reporting delayed (aged ≥16 years) vs normal age at menarche (OR = 1.66; P = 3.90E-07). Conclusion We have found evidence that functionally damaging variants in MC3R are overrepresented in individuals with CDGP but are not a common cause of this phenotype.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Endocrine Society
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Constitutional delayed of puberty
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MC3R
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Genes
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Endocrinología y Metabolismo
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Medicina Clínica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Prevalence of Deleterious Variants in MC3R in Patients With Constitutional Delay of Growth and Puberty
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2024-02-28T10:16:13Z
dc.journal.volume
108
dc.journal.number
12
dc.journal.pagination
e1580-e1587
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Oxford
dc.description.fil
Fil: Duckett, Katie. Addenbrooke’s Hospital; Reino Unido
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Fil: Williamson, Alice. Addenbrooke’s Hospital; Reino Unido
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Fil: Kincaid, John W. R.. Addenbrooke’s Hospital; Reino Unido
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Fil: Rainbow, Kara. Addenbrooke’s Hospital; Reino Unido
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Fil: Corbin, Laura J.. University of Bristol; Reino Unido
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Fil: Martin, Hilary C.. Wellcome Sanger Institute; Reino Unido
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Fil: Eberhardt, Ruth Y.. Wellcome Sanger Institute; Reino Unido
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Fil: Huang, Qin Qin. Wellcome Sanger Institute; Reino Unido
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Fil: Hurles, Matthew E.. Wellcome Sanger Institute; Reino Unido
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Fil: He, Wen. Boston Children’s Hospital; Estados Unidos
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Fil: Brauner, Raja. Umr - S1134 Biologie Integree Du Globule Rouge ; Universite de Paris;
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Fil: Delaney, Angela. St. Jude Children’s Research Hospital; Estados Unidos
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Fil: Dunkel, Leo. Barts & the London Medical School; Reino Unido
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Fil: Grinspon, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
dc.description.fil
Fil: Hall, Janet E. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
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Fil: Hirschhorn, Joel N.. Public Health Service. National Institute Of Health; Estados Unidos
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Fil: Howard, Sasha R.. Queen Mary University of London; Reino Unido
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Fil: Latronico, Ana C.. No especifíca;
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Fil: Jorge, Alexander A. L.. No especifíca;
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Fil: McElreavey, Ken. Universite de Paris; Francia
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Fil: Mericq, Verónica. Universidad de Chile; Chile
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Fil: Merino, Paulina M.. Universidad de Chile; Chile
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Fil: Palmert, Mark R.. University of Toronto; Canadá
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Fil: Plummer, Lacey. Massachusetts General Hospital Harvard; Estados Unidos
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Fil: Rey, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
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Fil: Rezende, Raíssa C.. No especifíca;
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Fil: Seminara, Stephanie B.. Massachusetts General Hospital Harvard; Estados Unidos
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Fil: Salnikov, Kathryn. Massachusetts General Hospital Harvard; Estados Unidos
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Fil: Banerjee, Indraneel. Royal Manchester Children’s Hospital; Reino Unido
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Fil: Lam, Brian Y. H.. Wellcome-MRC Institute of Metabolic Science; Reino Unido
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Fil: Perry, John R. B.. Wellcome-MRC Institute of Metabolic Science; Reino Unido
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Fil: Timpson, Nicholas J.. University of Bristol; Reino Unido
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Fil: Clayton, Peter. Royal Manchester Children’s Hospital; Reino Unido
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Fil: Chan, Yee Ming. Boston Children’s Hospital; Estados Unidos
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Fil: Ong, Ken K.. University of Cambridge; Estados Unidos
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Fil: O’Rahilly, Stephen. University of Cambridge; Estados Unidos
dc.journal.title
Journal of Clinical Endocrinology and Metabolism
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgad373/7204094
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1210/clinem/dgad373
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