Yonsei Med J.  2017 May;58(3):527-532. 10.3349/ymj.2017.58.3.527.

Rare Frequency of Mutations in Pituitary Transcription Factor Genes in Combined Pituitary Hormone or Isolated Growth Hormone Deficiencies in Korea

• Choi JH
• Jung CW
• Kang E
• Kim YM
• Heo SH
• Lee BH
• Kim GH
• Yoo HW

• KMID: 2419109
• DOI: http://doi.org/10.3349/ymj.2017.58.3.527

Abstract

PURPOSE
Congenital hypopituitarism is caused by mutations in pituitary transcription factors involved in the development of the hypothalamic-pituitary axis. Mutation frequencies of genes involved in congenital hypopituitarism are extremely low and vary substantially between ethnicities. This study was undertaken to compare the clinical, endocrinological, and radiological features of patients with an isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD).
MATERIALS AND METHODS
This study included 27 patients with sporadic IGHD and CPHD. A mutation analysis of the POU1F1, PROP1, LHX3, LHX4, and HESX1 genes was performed using genomic DNA from peripheral blood leukocytes.
RESULTS
IGHD and CPHD were observed in 4 and 23 patients, respectively. Mean age at diagnosis was 8.28±7.25 years for IGHD and 13.48±10.46 years for CPHD (p=0.37). Serum insulin-like growth factor-1 and peak growth hormone (GH) levels following GH stimulation tests were significantly lower in patients with CPHD than in those with IGHD (p<0.05). Sellar MRI findings revealed structural abnormalities in 3 patients with IGHD (75%) and 21 patients with CPHD (91.3%) (p=0.62). A mutation analysis identified homozygous p.R109Q mutations in HESX1 in a patient with CPHD. Patients with CPHD had more severe GHD than those with IGHD.
CONCLUSION
The frequency of defects in the genes encoding pituitary transcription factors was extremely low in Korean patients with congenital hypopituitarism. Environmental factors and the impact of other causative genes may contribute to this clinical phenotype.

Keyword

Combined pituitary hormone deficiency; HESX1; isolated growth hormone deficiency

MeSH Terms

Adolescent
Child
Child, Preschool
DNA Mutational Analysis
Dwarfism, Pituitary/blood/congenital/ethnology/*genetics
Female
Growth Hormone
Homozygote
Humans
Hypopituitarism/blood/*congenital/ethnology/genetics
Infant
Magnetic Resonance Imaging
Male
Mutation Rate
Phenotype
Republic of Korea/epidemiology
Transcription Factors/*genetics
Young Adult
Transcription Factors
Growth Hormone

Figure

• 

  Fig. 1 Partial sequences of the HESX1 gene in subject 21 with combined pituitary hormone deficiency. Mutation analysis identified homozygous c.326G>A (p.R109Q) mutations in HESX1. Both parents were phenotypically normal and heterozygous carriers of a p.R109Q mutation in HESX1. WT, wild-type.

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