Combined Growth Hormone and Thyroid-Stimulating Hormone Deficiency in a Japanese Patient with a Novel Frameshift Mutation in IGSF1

Yumi Asakura, Kiyomi Abe, Koji Muroya, Junko Hanakawa, Yuji Oto, Satoshi Narumi, Tomonobu Hasegawa, Masanori Adachi

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


Recent reports have indicated that loss-offunction mutations in the immunoglobulin superfamily member 1 gene ( IGSF1 , OMIM 300888) cause congenital central hypothyroidism with macroorchidism. Methods: We conducted a next-generation sequencing-based comprehensive mutation screening for pituitary hormone deficiencies to elucidate molecular mechanisms other than anatomical abnormalities of the pituitary that might be responsible for multiple anterior hormone deficiency in a male patient who originally visited our institute complaining of short stature. He was born large for gestational age (4,370 g, + 3.0 SD) after an obstructed labour. Endocrinological evaluation revealed growth hormone and thyroid-stimulating hormone deficiency. Magnetic resonance imaging showed a discontinuity of the pituitary stalk with an ectopic posterior lobe and a hypoplastic anterior lobe, likely explaining multiple anterior pituitary hormone deficiency. Result: We identified a novel hemizygous IGSF1 mutation (c.1137-1138delCA, p.Asn380Glnfs∗6) in the patient. In reviewing the literature, we noticed that all reported Japanese male IGSF1 mutation carriers were born larger than mean standards for gestational age (mean birth weight SD score of +2.0, 95% confidence interval 1.0-3.0). Conclusion: This case suggests that more attention should be paid to intrauterine growth and birth history when patients are suspected of having an IGSF1 mutation.

Original languageEnglish
Pages (from-to)349-354
Number of pages6
JournalHormone Research in Paediatrics
Issue number5
Publication statusPublished - 2015 Nov 1


  • Central hypothyroidism
  • Growth hormone deficiency
  • IGSF1
  • Invisible stalk
  • Large for gestational age

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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