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Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement
Congenital central hypothyroidism occurs either in isolation or in conjunction with other pituitary hormone deficits. Using exome and candidate gene sequencing, we identified eight distinct mutations and two deletions in IGSF1 in males from eleven unrelated families with central hypothyroidism, test...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511587/ https://www.ncbi.nlm.nih.gov/pubmed/23143598 http://dx.doi.org/10.1038/ng.2453 |
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author | Sun, Yu Bak, Beata Schoenmakers, Nadia van Trotsenburg, A.S. Paul Oostdijk, Wilma Voshol, Peter Cambridge, Emma White, Jacqueline K. le Tissier, Paul Gharavy, S. Neda Mousavy Martinez-Barbera, Juan P. Stokvis-Brantsma, Wilhelmina H. Vulsma, Thomas Kempers, Marlies J. Persani, Luca Campi, Irene Bonomi, Marco Beck-Peccoz, Paolo Zhu, Hongdong Davis, Timothy M.E. Hokken-Koelega, Anita C.S. Del Blanco, Daria Gorbenko Rangasami, Jayanti J. Ruivenkamp, Claudia A.L. Laros, Jeroen F.J. Kriek, Marjolein Kant, Sarina G. Bosch, Cathy A.J. Biermasz, Nienke R. Appelman-Dijkstra, Natasha M. Corssmit, Eleonora P. Hovens, Guido C.J. Pereira, Alberto M. den Dunnen, Johan T. Wade, Michael G. Breuning, Martijn H. Hennekam, Raoul C. Chatterjee, Krishna Dattani, Mehul T. Wit, Jan M. Bernard, Daniel J. |
author_facet | Sun, Yu Bak, Beata Schoenmakers, Nadia van Trotsenburg, A.S. Paul Oostdijk, Wilma Voshol, Peter Cambridge, Emma White, Jacqueline K. le Tissier, Paul Gharavy, S. Neda Mousavy Martinez-Barbera, Juan P. Stokvis-Brantsma, Wilhelmina H. Vulsma, Thomas Kempers, Marlies J. Persani, Luca Campi, Irene Bonomi, Marco Beck-Peccoz, Paolo Zhu, Hongdong Davis, Timothy M.E. Hokken-Koelega, Anita C.S. Del Blanco, Daria Gorbenko Rangasami, Jayanti J. Ruivenkamp, Claudia A.L. Laros, Jeroen F.J. Kriek, Marjolein Kant, Sarina G. Bosch, Cathy A.J. Biermasz, Nienke R. Appelman-Dijkstra, Natasha M. Corssmit, Eleonora P. Hovens, Guido C.J. Pereira, Alberto M. den Dunnen, Johan T. Wade, Michael G. Breuning, Martijn H. Hennekam, Raoul C. Chatterjee, Krishna Dattani, Mehul T. Wit, Jan M. Bernard, Daniel J. |
author_sort | Sun, Yu |
collection | PubMed |
description | Congenital central hypothyroidism occurs either in isolation or in conjunction with other pituitary hormone deficits. Using exome and candidate gene sequencing, we identified eight distinct mutations and two deletions in IGSF1 in males from eleven unrelated families with central hypothyroidism, testicular enlargement, and variably low prolactin concentrations. IGSF1 is a membrane glycoprotein highly expressed in the anterior pituitary gland and the identified mutations impair its trafficking to the cell surface in heterologous cells. Igsf1-deficient male mice show diminished pituitary and serum thyroid-stimulating hormone (TSH) concentrations, reduced pituitary thyrotropin-releasing hormone (TRH) receptor expression, decreased triiodothyronine concentrations, and increased body mass. Collectively, our observations delineate a novel X-linked disorder in which loss-of-function mutations in IGSF1 cause central hypothyroidism, likely secondary to an associated impairment in pituitary TRH signaling. |
format | Online Article Text |
id | pubmed-3511587 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
record_format | MEDLINE/PubMed |
spelling | pubmed-35115872013-06-01 Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement Sun, Yu Bak, Beata Schoenmakers, Nadia van Trotsenburg, A.S. Paul Oostdijk, Wilma Voshol, Peter Cambridge, Emma White, Jacqueline K. le Tissier, Paul Gharavy, S. Neda Mousavy Martinez-Barbera, Juan P. Stokvis-Brantsma, Wilhelmina H. Vulsma, Thomas Kempers, Marlies J. Persani, Luca Campi, Irene Bonomi, Marco Beck-Peccoz, Paolo Zhu, Hongdong Davis, Timothy M.E. Hokken-Koelega, Anita C.S. Del Blanco, Daria Gorbenko Rangasami, Jayanti J. Ruivenkamp, Claudia A.L. Laros, Jeroen F.J. Kriek, Marjolein Kant, Sarina G. Bosch, Cathy A.J. Biermasz, Nienke R. Appelman-Dijkstra, Natasha M. Corssmit, Eleonora P. Hovens, Guido C.J. Pereira, Alberto M. den Dunnen, Johan T. Wade, Michael G. Breuning, Martijn H. Hennekam, Raoul C. Chatterjee, Krishna Dattani, Mehul T. Wit, Jan M. Bernard, Daniel J. Nat Genet Article Congenital central hypothyroidism occurs either in isolation or in conjunction with other pituitary hormone deficits. Using exome and candidate gene sequencing, we identified eight distinct mutations and two deletions in IGSF1 in males from eleven unrelated families with central hypothyroidism, testicular enlargement, and variably low prolactin concentrations. IGSF1 is a membrane glycoprotein highly expressed in the anterior pituitary gland and the identified mutations impair its trafficking to the cell surface in heterologous cells. Igsf1-deficient male mice show diminished pituitary and serum thyroid-stimulating hormone (TSH) concentrations, reduced pituitary thyrotropin-releasing hormone (TRH) receptor expression, decreased triiodothyronine concentrations, and increased body mass. Collectively, our observations delineate a novel X-linked disorder in which loss-of-function mutations in IGSF1 cause central hypothyroidism, likely secondary to an associated impairment in pituitary TRH signaling. 2012-11-11 2012-12 /pmc/articles/PMC3511587/ /pubmed/23143598 http://dx.doi.org/10.1038/ng.2453 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Sun, Yu Bak, Beata Schoenmakers, Nadia van Trotsenburg, A.S. Paul Oostdijk, Wilma Voshol, Peter Cambridge, Emma White, Jacqueline K. le Tissier, Paul Gharavy, S. Neda Mousavy Martinez-Barbera, Juan P. Stokvis-Brantsma, Wilhelmina H. Vulsma, Thomas Kempers, Marlies J. Persani, Luca Campi, Irene Bonomi, Marco Beck-Peccoz, Paolo Zhu, Hongdong Davis, Timothy M.E. Hokken-Koelega, Anita C.S. Del Blanco, Daria Gorbenko Rangasami, Jayanti J. Ruivenkamp, Claudia A.L. Laros, Jeroen F.J. Kriek, Marjolein Kant, Sarina G. Bosch, Cathy A.J. Biermasz, Nienke R. Appelman-Dijkstra, Natasha M. Corssmit, Eleonora P. Hovens, Guido C.J. Pereira, Alberto M. den Dunnen, Johan T. Wade, Michael G. Breuning, Martijn H. Hennekam, Raoul C. Chatterjee, Krishna Dattani, Mehul T. Wit, Jan M. Bernard, Daniel J. Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement |
title | Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement |
title_full | Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement |
title_fullStr | Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement |
title_full_unstemmed | Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement |
title_short | Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement |
title_sort | loss-of-function mutations in igsf1 cause an x-linked syndrome of central hypothyroidism and testicular enlargement |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511587/ https://www.ncbi.nlm.nih.gov/pubmed/23143598 http://dx.doi.org/10.1038/ng.2453 |
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