Cargando…

Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures

OBJECTIVE: Congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) represent rare and common forms of GnRH deficiency, respectively. Both CDGP and CHH present with delayed puberty, and the distinction between these two entities during early adolescence is...

Descripción completa

Detalles Bibliográficos
Autores principales: Cassatella, Daniele, Howard, Sasha R, Acierno, James S, Xu, Cheng, Papadakis, Georgios E, Santoni, Federico A, Dwyer, Andrew A, Santini, Sara, Sykiotis, Gerasimos P, Chambion, Caroline, Meylan, Jenny, Marino, Laura, Favre, Lucie, Li, Jiankang, Liu, Xuanzhu, Zhang, Jianguo, Bouloux, Pierre-Marc, Geyter, Christian De, Paepe, Anne De, Dhillo, Waljit S, Ferrara, Jean-Marc, Hauschild, Michael, Lang-Muritano, Mariarosaria, Lemke, Johannes R, Flück, Christa, Nemeth, Attila, Phan-Hug, Franziska, Pignatelli, Duarte, Popovic, Vera, Pekic, Sandra, Quinton, Richard, Szinnai, Gabor, l’Allemand, Dagmar, Konrad, Daniel, Sharif, Saba, Iyidir, Özlem Turhan, Stevenson, Brian J, Yang, Huanming, Dunkel, Leo, Pitteloud, Nelly
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863472/
https://www.ncbi.nlm.nih.gov/pubmed/29419413
http://dx.doi.org/10.1530/EJE-17-0568
_version_ 1783308397465042944
author Cassatella, Daniele
Howard, Sasha R
Acierno, James S
Xu, Cheng
Papadakis, Georgios E
Santoni, Federico A
Dwyer, Andrew A
Santini, Sara
Sykiotis, Gerasimos P
Chambion, Caroline
Meylan, Jenny
Marino, Laura
Favre, Lucie
Li, Jiankang
Liu, Xuanzhu
Zhang, Jianguo
Bouloux, Pierre-Marc
Geyter, Christian De
Paepe, Anne De
Dhillo, Waljit S
Ferrara, Jean-Marc
Hauschild, Michael
Lang-Muritano, Mariarosaria
Lemke, Johannes R
Flück, Christa
Nemeth, Attila
Phan-Hug, Franziska
Pignatelli, Duarte
Popovic, Vera
Pekic, Sandra
Quinton, Richard
Szinnai, Gabor
l’Allemand, Dagmar
Konrad, Daniel
Sharif, Saba
Iyidir, Özlem Turhan
Stevenson, Brian J
Yang, Huanming
Dunkel, Leo
Pitteloud, Nelly
author_facet Cassatella, Daniele
Howard, Sasha R
Acierno, James S
Xu, Cheng
Papadakis, Georgios E
Santoni, Federico A
Dwyer, Andrew A
Santini, Sara
Sykiotis, Gerasimos P
Chambion, Caroline
Meylan, Jenny
Marino, Laura
Favre, Lucie
Li, Jiankang
Liu, Xuanzhu
Zhang, Jianguo
Bouloux, Pierre-Marc
Geyter, Christian De
Paepe, Anne De
Dhillo, Waljit S
Ferrara, Jean-Marc
Hauschild, Michael
Lang-Muritano, Mariarosaria
Lemke, Johannes R
Flück, Christa
Nemeth, Attila
Phan-Hug, Franziska
Pignatelli, Duarte
Popovic, Vera
Pekic, Sandra
Quinton, Richard
Szinnai, Gabor
l’Allemand, Dagmar
Konrad, Daniel
Sharif, Saba
Iyidir, Özlem Turhan
Stevenson, Brian J
Yang, Huanming
Dunkel, Leo
Pitteloud, Nelly
author_sort Cassatella, Daniele
collection PubMed
description OBJECTIVE: Congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) represent rare and common forms of GnRH deficiency, respectively. Both CDGP and CHH present with delayed puberty, and the distinction between these two entities during early adolescence is challenging. More than 30 genes have been implicated in CHH, while the genetic basis of CDGP is poorly understood. DESIGN: We characterized and compared the genetic architectures of CHH and CDGP, to test the hypothesis of a shared genetic basis between these disorders. METHODS: Exome sequencing data were used to identify rare variants in known genes in CHH (n = 116), CDGP (n = 72) and control cohorts (n = 36 874 ExAC and n = 405 CoLaus). RESULTS: Mutations in at least one CHH gene were found in 51% of CHH probands, which is significantly higher than in CDGP (7%, P = 7.6 × 10(−11)) or controls (18%, P = 5.5 × 10(−12)). Similarly, oligogenicity (defined as mutations in more than one gene) was common in CHH patients (15%) relative to CDGP (1.4%, P = 0.002) and controls (2%, P = 6.4 × 10(−7)). CONCLUSIONS: Our data suggest that CDGP and CHH have distinct genetic profiles, and this finding may facilitate the differential diagnosis in patients presenting with delayed puberty.
format Online
Article
Text
id pubmed-5863472
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Bioscientifica Ltd
record_format MEDLINE/PubMed
spelling pubmed-58634722018-03-23 Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures Cassatella, Daniele Howard, Sasha R Acierno, James S Xu, Cheng Papadakis, Georgios E Santoni, Federico A Dwyer, Andrew A Santini, Sara Sykiotis, Gerasimos P Chambion, Caroline Meylan, Jenny Marino, Laura Favre, Lucie Li, Jiankang Liu, Xuanzhu Zhang, Jianguo Bouloux, Pierre-Marc Geyter, Christian De Paepe, Anne De Dhillo, Waljit S Ferrara, Jean-Marc Hauschild, Michael Lang-Muritano, Mariarosaria Lemke, Johannes R Flück, Christa Nemeth, Attila Phan-Hug, Franziska Pignatelli, Duarte Popovic, Vera Pekic, Sandra Quinton, Richard Szinnai, Gabor l’Allemand, Dagmar Konrad, Daniel Sharif, Saba Iyidir, Özlem Turhan Stevenson, Brian J Yang, Huanming Dunkel, Leo Pitteloud, Nelly Eur J Endocrinol Clinical Study OBJECTIVE: Congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) represent rare and common forms of GnRH deficiency, respectively. Both CDGP and CHH present with delayed puberty, and the distinction between these two entities during early adolescence is challenging. More than 30 genes have been implicated in CHH, while the genetic basis of CDGP is poorly understood. DESIGN: We characterized and compared the genetic architectures of CHH and CDGP, to test the hypothesis of a shared genetic basis between these disorders. METHODS: Exome sequencing data were used to identify rare variants in known genes in CHH (n = 116), CDGP (n = 72) and control cohorts (n = 36 874 ExAC and n = 405 CoLaus). RESULTS: Mutations in at least one CHH gene were found in 51% of CHH probands, which is significantly higher than in CDGP (7%, P = 7.6 × 10(−11)) or controls (18%, P = 5.5 × 10(−12)). Similarly, oligogenicity (defined as mutations in more than one gene) was common in CHH patients (15%) relative to CDGP (1.4%, P = 0.002) and controls (2%, P = 6.4 × 10(−7)). CONCLUSIONS: Our data suggest that CDGP and CHH have distinct genetic profiles, and this finding may facilitate the differential diagnosis in patients presenting with delayed puberty. Bioscientifica Ltd 2018-02-01 /pmc/articles/PMC5863472/ /pubmed/29419413 http://dx.doi.org/10.1530/EJE-17-0568 Text en © 2018 The authors http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Clinical Study
Cassatella, Daniele
Howard, Sasha R
Acierno, James S
Xu, Cheng
Papadakis, Georgios E
Santoni, Federico A
Dwyer, Andrew A
Santini, Sara
Sykiotis, Gerasimos P
Chambion, Caroline
Meylan, Jenny
Marino, Laura
Favre, Lucie
Li, Jiankang
Liu, Xuanzhu
Zhang, Jianguo
Bouloux, Pierre-Marc
Geyter, Christian De
Paepe, Anne De
Dhillo, Waljit S
Ferrara, Jean-Marc
Hauschild, Michael
Lang-Muritano, Mariarosaria
Lemke, Johannes R
Flück, Christa
Nemeth, Attila
Phan-Hug, Franziska
Pignatelli, Duarte
Popovic, Vera
Pekic, Sandra
Quinton, Richard
Szinnai, Gabor
l’Allemand, Dagmar
Konrad, Daniel
Sharif, Saba
Iyidir, Özlem Turhan
Stevenson, Brian J
Yang, Huanming
Dunkel, Leo
Pitteloud, Nelly
Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures
title Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures
title_full Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures
title_fullStr Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures
title_full_unstemmed Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures
title_short Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures
title_sort congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures
topic Clinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863472/
https://www.ncbi.nlm.nih.gov/pubmed/29419413
http://dx.doi.org/10.1530/EJE-17-0568
work_keys_str_mv AT cassatelladaniele congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT howardsashar congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT aciernojamess congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT xucheng congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT papadakisgeorgiose congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT santonifedericoa congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT dwyerandrewa congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT santinisara congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT sykiotisgerasimosp congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT chambioncaroline congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT meylanjenny congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT marinolaura congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT favrelucie congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT lijiankang congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT liuxuanzhu congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT zhangjianguo congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT boulouxpierremarc congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT geyterchristiande congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT paepeannede congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT dhillowaljits congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT ferrarajeanmarc congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT hauschildmichael congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT langmuritanomariarosaria congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT lemkejohannesr congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT fluckchrista congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT nemethattila congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT phanhugfranziska congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT pignatelliduarte congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT popovicvera congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT pekicsandra congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT quintonrichard congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT szinnaigabor congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT lallemanddagmar congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT konraddaniel congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT sharifsaba congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT iyidirozlemturhan congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT stevensonbrianj congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT yanghuanming congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT dunkelleo congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures
AT pitteloudnelly congenitalhypogonadotropichypogonadismandconstitutionaldelayofgrowthandpubertyhavedistinctgeneticarchitectures