Article (Scientific journals)
Gigantism and Acromegaly Due to Xq26 Microduplications and GPR101 Mutation.
Trivellin, Giampaolo; Daly, Adrian; Faucz, Fabio R. et al.
2014In New England Journal of Medicine
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Abstract :
[en] Background Increased secretion of growth hormone leads to gigantism in children and acromegaly in adults; the genetic causes of gigantism and acromegaly are poorly understood. Methods We performed clinical and genetic studies of samples obtained from 43 patients with gigantism and then sequenced an implicated gene in samples from 248 patients with acromegaly. Results We observed microduplication on chromosome Xq26.3 in samples from 13 patients with gigantism; of these samples, 4 were obtained from members of two unrelated kindreds, and 9 were from patients with sporadic cases. All the patients had disease onset during early childhood. Of the patients with gigantism who did not carry an Xq26.3 microduplication, none presented before the age of 5 years. Genomic characterization of the Xq26.3 region suggests that the microduplications are generated during chromosome replication and that they contain four protein-coding genes. Only one of these genes, GPR101, which encodes a G-protein-coupled receptor, was overexpressed in patients' pituitary lesions. We identified a recurrent GPR101 mutation (p.E308D) in 11 of 248 patients with acromegaly, with the mutation found mostly in tumors. When the mutation was transfected into rat GH3 cells, it led to increased release of growth hormone and proliferation of growth hormone-producing cells. Conclusions We describe a pediatric disorder (which we have termed X-linked acrogigantism [X-LAG]) that is caused by an Xq26.3 genomic duplication and is characterized by early-onset gigantism resulting from an excess of growth hormone. Duplication of GPR101 probably causes X-LAG. We also found a recurrent mutation in GPR101 in some adults with acromegaly. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Trivellin, Giampaolo 
Daly, Adrian   ;  Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Faucz, Fabio R.
Yuan, Bo
Rostomyan, Liliya  ;  Université de Liège - ULiège > CHU - @chu - AD
Larco, Darwin O.
Schernthaner-Reiter, Marie Helene
Szarek, Eva
Leal, Leticia F.
CABERG, Jean-Hubert ;  Centre Hospitalier Universitaire de Liège - CHU > Génétique
CASTERMANS, Emilie ;  Centre Hospitalier Universitaire de Liège - CHU > Génétique
Villa, Chiara
Dimopoulos, Aggeliki
Chittiboina, Prashant
Xekouki, Paraskevi
Shah, Nalini S.
Metzger, Daniel
Lysy, Philippe A.
Ferrante, Emanuele
Strebkova, Natalia
Mazerkina, Nadia
Zatelli, Maria Chiara
Lodish, Maya
Horvath, Anelia
de Alexandre, Rodrigo Bertollo
Manning, Allison D.
Levy, Isaac
Keil, Margaret F.
Sierra, Maria De La Luz
Palmeira, Leonor ;  Université de Liège - ULiège > Département de productions animales > GIGA-R : Génomique animale
Coppieters, Wouter ;  Université de Liège - ULiège > Département de productions animales > GIGA-R : Génomique animale
Georges, Michel  ;  Université de Liège - ULiège > Département de productions animales > GIGA-R : Génomique animale
Naves, Luciana Ansaneli
JAMAR, Mauricette ;  Centre Hospitalier Universitaire de Liège - CHU > Génétique
Bours, Vincent ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine
Wu, T. John
Choong, Catherine S.
Bertherat, Jerome
Chanson, Philippe
Kamenicky, Peter
Farrell, William E.
Barlier, Anne
Quezado, Martha
Bjelobaba, Ivana
Stojilkovic, Stanko S.
Wess, Jurgen
Costanzi, Stefano
Liu, Pengfei
Lupski, James R.
Beckers, Albert  ;  Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Stratakis, Constantine A. 
More authors (41 more) Less
 These authors have contributed equally to this work.
Language :
English
Title :
Gigantism and Acromegaly Due to Xq26 Microduplications and GPR101 Mutation.
Publication date :
2014
Journal title :
New England Journal of Medicine
ISSN :
0028-4793
eISSN :
1533-4406
Publisher :
Massachusetts Medical Society, United States - Massachusetts
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 18 December 2014

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