A novel dominant negative mutation of OTX2 associated with combined pituitary hormone deficiency.

The Journal of Clinical Endocrinology and Metabolism
Daniel DiaczokSally Radovick

Abstract

Combined pituitary hormone deficiency (CPHD) is characterized by deficiencies in more than one anterior pituitary hormone. Mutations in developmental factors responsible for pituitary cell specification and gene expression have been found in CPHD patients. OTX2, a bicoid class homeodomain protein, is necessary for both forebrain development and transactivation of the HESX1 promoter, but as of yet, has not been associated with CPHD. The goal of this study was to identify and characterize novel mutations in pituitary specific transcription factors from CPHD patients. Genomic DNA was isolated from patients with hypopituitarism to amplify and sequence eight pituitary specific transcription factors (HESX1, LHX3, LHX4, OTX2, PITX2, POU1F1, PROP1, and SIX6). Characterization of novel mutations is based on structural and functional studies. We describe two unrelated children with CPHD who presented with neonatal hypoglycemia, and deficiencies of GH, TSH, LH, FSH, and ACTH. Magnetic resonance imaging revealed anterior pituitary hypoplasia with an ectopic posterior pituitary. A novel heterozygous OTX2 mutation (N233S) was identified. Wild-type and mutant OTX2 proteins bind equivalently to bicoid binding sites, whereas mutant OTX2 reveale...Continue Reading

References

Apr 1, 1991·Journal of Medical Genetics·C P BennettM J Seller
Nov 1, 1995·Genes & Development·I MatsuoS Aizawa
Mar 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·I BachM G Rosenfeld
Nov 1, 1995·Mammalian Genome : Official Journal of the International Mammalian Genome Society·M MbikayE M Simpson
May 30, 1998·American Journal of Medical Genetics·E LemyreM Lambert
Jan 7, 2000·Biochemical and Biophysical Research Communications·T NakanoS Aizawa
Jun 14, 2000·Clinical Genetics·M T Dattani, I C Robinson
Dec 13, 2000·Proceedings of the National Academy of Sciences of the United States of America·L ZakinP Brulet
Aug 16, 2001·Molecular Biology and Evolution·A GermotS Mazan
Aug 31, 2002·Endocrine Reviews·Laurie E Cohen, Sally Radovick
Mar 29, 2003·The Journal of Biological Chemistry·Juan Ramón Martínez-MoralesSimon Saule
Aug 29, 2003·Development·Michael E ZuberWilliam A Harris
Oct 15, 2003·The Journal of Clinical Endocrinology and Metabolism·Ronald N CohenSally Radovick
Oct 17, 2003·The Journal of Clinical Investigation·Luciani R CarvalhoMehul T Dattani
Nov 20, 2003·Nature Neuroscience·Akihiro NishidaTakahisa Furukawa
Apr 23, 2005·American Journal of Human Genetics·Nicola K RaggeIsabel M Hanson
May 13, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Bertrand VernaySiew-Lan Ang
Jul 13, 2006·American Journal of Medical Genetics. Part a·Leisha D NolenRobyn V Jamieson
Jul 18, 2006·EMBO Reports·Nicolas FossatThomas Lamonerie
Oct 25, 2006·Molecular and Cellular Biology·Thomas HeimbucherThomas Czerny
Dec 7, 2006·The Journal of Clinical Endocrinology and Metabolism·David E G McNayMehul T Dattani
Apr 5, 2007·European Journal of Human Genetics : EJHG·R Alex HendersonVeronica van Heyningen

❮ Previous
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Citations

Jul 27, 2011·Nature Reviews. Endocrinology·Kelly L PrinceSimon J Rhodes
Apr 30, 2009·The Journal of Biological Chemistry·Rachel Larder, Pamela L Mellon
Aug 11, 2011·Physiological Genomics·Amanda H MortensenSally A Camper
Oct 20, 2009·Endocrine Reviews·Daniel KelbermanMehul T Dattani
Mar 26, 2011·Molecular Endocrinology·Daniel DiaczokSally Radovick
May 13, 2014·PloS One·Dina ZielinskiYaniv Erlich
Dec 1, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Horacio J NovairaSally Radovick
Aug 9, 2012·The Journal of Endocrinology·Débora Cristina de MoraesTânia Maria Ortiga-Carvalho
Jun 21, 2012·European Journal of Endocrinology·Darya Gorbenko Del BlancoAnita C S Hokken-Koelega
Dec 6, 2011·Indian Journal of Pediatrics·Kyriaki S Alatzoglou, Mehul T Dattani
Jul 7, 2015·Clinical Endocrinology·Francesca De RienzoUNKNOWN Italian Study Group on Genetics of CPHD
Mar 15, 2011·Best Practice & Research. Clinical Endocrinology & Metabolism·Mark James McCabeMehul T Dattani
Oct 27, 2009·Trends in Endocrinology and Metabolism : TEM·Christopher J RomeroSally Radovick
Sep 19, 2009·Early Human Development·Kyriaki S Alatzoglou, Mehul T Dattani
May 7, 2009·Stem Cells·Jianghai ChenHugo Vankelecom
May 15, 2012·American Journal of Medical Genetics. Part a·Aimé LumakaKoen Devriendt
Oct 1, 2011·Clinical Endocrinology·Natascia Di IorgiMohamad Maghnie
Dec 15, 2010·The European Journal of Neuroscience·Hugo Vankelecom
Feb 6, 2014·Molecular Genetics & Genomic Medicine·Christina Gerth-KahlertDavid R Fitzpatrick
May 18, 2013·Xenotransplantation·Aliakbar Haddad-MashadrizehMadjid Momeni-Moghaddam
May 22, 2010·Clinical Genetics·K F SchilterE V Semina
May 27, 2014·European Journal of Medical Genetics·Kathleen A Williamson, David R FitzPatrick
Jul 3, 2013·Molecular and Cellular Endocrinology·Rachel LarderPamela L Mellon
Jun 18, 2015·Molecular Neurobiology·H J NovairaS Radovick
Apr 17, 2015·Journal of Molecular Endocrinology·Ivo J P ArnholdAlexander A L Jorge
Oct 16, 2014·Human Molecular Genetics·Amanda H MortensenSally A Camper
Oct 19, 2011·Molecular Genetics and Metabolism·Anne M Slavotinek
Mar 26, 2013·Experimental Eye Research·Francis Beby, Thomas Lamonerie
Sep 10, 2014·Journal of Endocrinological Investigation·F CastinettiT Brue
Dec 14, 2016·Human Mutation·Sirawit IttisoponpisanAlessia David
Apr 8, 2017·Ophthalmic Genetics·Puneeth H SomashekarKatta M Girisha
Apr 13, 2017·The Journal of Clinical Endocrinology and Metabolism·Anu BashambooRaja Brauner
Sep 30, 2015·The Journal of Endocrinology·Nadia SchoenmakersMehul T Dattani
Nov 10, 2016·Endocrine Reviews·Qing FangSally A Camper
Aug 6, 2010·The Journal of Clinical Endocrinology and Metabolism·Marcela M FrançaIvo J P Arnhold
Dec 14, 2011·Current Opinion in Endocrinology, Diabetes, and Obesity·Laurie E Cohen
Nov 9, 2019·The Journal of Clinical Endocrinology and Metabolism·Louise Cheryl Gregory, Mehul Tulsidas Dattani
Dec 8, 2009·The Journal of Clinical Endocrinology and Metabolism·Sumito DatekiTsutomu Ogata
Dec 18, 2019·The Journal of Clinical Investigation·Ryusaku MatsumotoYutaka Takahashi
Dec 15, 2020·World Journal of Gastroenterology : WJG·Ze-Yu WuBing Chang

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