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


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.


CONCLUSIONS
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.
Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
Jin Ho
JH
Choi
Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
Chang Woo
CW
Jung
Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
Eungu
E
Kang
Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
Yoon Myung
YM
Kim
Asan Institute for Life Sciences, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
Sun Hee
SH
Heo
Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
Beom Hee
BH
Lee
Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
Gu Hwan
GH
Kim
Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea. hwyoo@amc.seoul.kr.
Han Wook
HW
Yoo
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004393:Dwarfism, Pituitary / Q000097:blood / Q000151:congenital / Q000208:ethnology / Q000235:genetics*; D005260:Female; D013006:Growth Hormone; D006720:Homozygote; D006801:Humans; D007018:Hypopituitarism / Q000097:blood / Q000151:congenital* / Q000208:ethnology / Q000235:genetics; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D059645:Mutation Rate; D010641:Phenotype; D056910:Republic of Korea / Q000453:epidemiology; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
D014157:Transcription Factors; D013006:Growth Hormone
Combined pituitary hormone deficiency; HESX1; isolated growth hormone deficiency