A novel mutation in HESX1 causes combined pituitary hormone deficiency without septo optic dysplasia phenotypes

Endocrine Journal
Masaki TakagiTomonobu Hasegawa

Abstract

Heterozygous and/or homozygous HESX1 mutations have been reported to cause isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD), in association with septo optic dysplasia (SOD). We report a novel heterozygous HESX1 mutation in a CPHD patient without SOD phenotypes. The propositus was a one-year-old Japanese girl. Shortly after birth, she was found to be hypoglycemic. She was diagnosed with central adrenal insufficiency based on low cortisol and ACTH at a time of severe hypoglycemia. Further endocrine studies indicated that the patient also had central hypothyroidism and growth hormone deficiency. Using a next-generation sequencing strategy, we identified a novel heterozygous HESX1 mutation, c.326G>A (p.Arg109Gln). Western blotting and subcellular localization revealed no significant difference between wild type and mutant HESX1. Electrophoretic mobility shift assays showed that the mutant HESX1 abrogated DNA-binding ability. Mutant HESX1 was unable to repress PROP1-mediated activation. In conclusion, this study identified Arg109 as a critical residue in the HESX1 protein and extends our understanding of the phenotypic features, molecular mechanism, and developmental course associated with mu...Continue Reading

References

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
Dec 7, 2006·The Journal of Clinical Endocrinology and Metabolism·David E G McNayMehul T Dattani
Oct 20, 2009·Endocrine Reviews·Daniel KelbermanMehul T Dattani
Oct 27, 2009·Trends in Endocrinology and Metabolism : TEM·Christopher J RomeroSally Radovick
Mar 15, 2011·Best Practice & Research. Clinical Endocrinology & Metabolism·R Pfäffle, J Klammt
Feb 10, 2012·The Journal of Clinical Endocrinology and Metabolism·Taneli RaivioNelly Pitteloud
Apr 3, 2012·The Journal of Clinical Endocrinology and Metabolism·Rachel ReynaudThierry Brue
Feb 7, 2013·The Journal of Clinical Endocrinology and Metabolism·Mark J McCabeMehul T Dattani
Mar 8, 2013·Fertility and Sterility·Kayce NewbernLawrence C Layman
Aug 20, 2014·The Journal of Clinical Endocrinology and Metabolism·Toshikatsu MitsuiTomonobu Hasegawa
Jan 1, 2014·Human Genome Variation·Masaki TakagiTomonobu Hasegawa

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Citations

Mar 28, 2018·Human Molecular Genetics·Sungkook HongMaximilian Muenke
Mar 17, 2017·F1000Research·Mareike R StiegAnna Kopczak
Mar 18, 2021·The Journal of Clinical Endocrinology and Metabolism·Sebastian Alexis VishnopolskaMaria Ines Pérez-Millán

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