title: Combined Growth Hormone and Thyroid-Stimulating Hormone Deficiency in a Japanese Patient with a Novel Frameshift Mutation in IGSF1.
abstract: BACKGROUND
  Recent reports have indicated that loss-of-function 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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  This case suggests that more attention should be paid to intrauterine growth and birth history when patients are suspected of having an IGSF1 mutation.
authors: Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan.
authors: Yumi
authors: Y
authors: Asakura
authors: Kiyomi
authors: K
authors: Abe
authors: Koji
authors: K
authors: Muroya
authors: Junko
authors: J
authors: Hanakawa
authors: Yuji
authors: Y
authors: Oto
authors: Satoshi
authors: S
authors: Narumi
authors: Tomonobu
authors: T
authors: Hasegawa
authors: Masanori
authors: M
authors: Adachi
mesh_terms: D000293:Adolescent; D001724:Birth Weight / Q000235:genetics; D003409:Congenital Hypothyroidism / Q000235:genetics; D005260:Female; D005333:Fetus / Q000473:pathology; D016368:Frameshift Mutation / Q000235:genetics; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000473:pathology; D007037:Hypothyroidism; D007136:Immunoglobulins / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D007744:Obstetric Labor Complications; D010902:Pituitary Gland / Q000473:pathology; D011247:Pregnancy; D013972:Thyrotropin / Q000172:deficiency*
chemical_list: C112314:IGSF1 protein, human; D007136:Immunoglobulins; D008565:Membrane Proteins; D019382:Human Growth Hormone; D013972:Thyrotropin