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

Masaki Takagi, Mai Takahashi, Yoshiaki Ohtsu, Takeshi Sato, Satoshi Narumi, Hirokazu Arakawa, Tomonobu Hasegawa

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 oneyear- 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 mutations in HESX1. When multiple genes need to be analyzed for mutations simultaneously, targeted sequence analysis of interesting genomic regions is an attractive approach.

Original languageEnglish
Pages (from-to)405-410
Number of pages6
JournalEndocrine Journal
Volume63
Issue number4
DOIs
Publication statusPublished - 2016 Apr 25

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Septo-Optic Dysplasia
Phenotype
Mutation
Pituitary Dwarfism
Adrenal Insufficiency
Electrophoretic Mobility Shift Assay
Hypothyroidism
Hypoglycemia
Hypoglycemic Agents
Adrenocorticotropic Hormone
Growth Hormone
Sequence Analysis
Hydrocortisone
Western Blotting
Combined Pituitary Hormone Deficiency
Parturition
DNA
Genes
Proteins

Keywords

  • Combined pituitary hormone deficiency
  • HESX1
  • Homeobox
  • Targeted next-generation sequencing

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

A novel mutation in HESX1 causes combined pituitary hormone deficiency without septo optic dysplasia phenotypes. / Takagi, Masaki; Takahashi, Mai; Ohtsu, Yoshiaki; Sato, Takeshi; Narumi, Satoshi; Arakawa, Hirokazu; Hasegawa, Tomonobu.

In: Endocrine Journal, Vol. 63, No. 4, 25.04.2016, p. 405-410.

Research output: Contribution to journalArticle

Takagi, Masaki ; Takahashi, Mai ; Ohtsu, Yoshiaki ; Sato, Takeshi ; Narumi, Satoshi ; Arakawa, Hirokazu ; Hasegawa, Tomonobu. / A novel mutation in HESX1 causes combined pituitary hormone deficiency without septo optic dysplasia phenotypes. In: Endocrine Journal. 2016 ; Vol. 63, No. 4. pp. 405-410.
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