title: Novel compound heterozygous mutations in the SBP2 gene: characteristic clinical manifestations and the implications of GH and triiodothyronine in longitudinal bone growth and maturation.
abstract: OBJECTIVE
  Mutations in the selenocysteine insertion sequence binding protein 2 gene (SECISBP2 also known as SBP2) lead to a multisystemic disorder. Our objectives are to examine the clinical manifestations of the present patient and evaluate the effects of GH and triiodothyronine (T(3)) for longitudinal bone growth and maturation.
  
  
  METHODS
  A Japanese boy presented with unusual thyroid function tests (normal or slightly elevated TSH, low-normal or slightly decreased free T(3) (FT(3)), and elevated free thyroxine (FT(4))), short stature without GH deficiency, and delayed bone maturation. The entire coding region of the patient's SBP2 was analyzed. GH treatment was initiated when the patient was 4 years old, and combination therapy with GH plus T(3) was started when the patient was 10 years old. We monitored the patient's height and bone age until he was 11 years old.
  
  
  RESULTS
  The patient showed typical symptoms of SBP2 deficiency, and novel compound heterozygous mutations were identified in SBP2 (p.M515fsX563/p.Q79X). Six years of GH monotherapy improved the patient's height s.d. from -3.4 to -1.7 without accelerating bone maturation, whereas 6 months of T(3) treatment combined with GH almost normalized the thyroid function tests and improved both longitudinal bone growth and maturation.
  
  
  CONCLUSIONS
  In the growth plate, GH may compensate for decreased local T(3) effects on longitudinal bone growth; however, GH does not appear to compensate for the effects of T(3) on bone maturation. We believe that the present case has important implications for understanding the mechanism of thyroid hormone and GH on longitudinal bone growth and maturation.
authors.affiliation: Department of Pediatric Endocrinology and Metabolism, Aichi Children's Health and Medical Center, 1-2 Osakada, Morioka-cho, Obu, Aichi, Japan. takabeachisland@nifty.com
authors.forename: Takashi
authors.initials: T
authors.lastname: Hamajima
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Mushimoto
authors.forename: Hironori
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Kazumichi
authors.initials: K
authors.lastname: Onigata
mesh_terms: D000365:Age Determination by Skeleton; D001846:Bone Development / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D002113:Calcification, Physiologic / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D002675:Child, Preschool; D006130:Growth Disorders / Q000188:drug therapy / Q000235:genetics; D006579:Heterozygote; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009154:Mutation / Q000502:physiology; D010375:Pedigree; D016601:RNA-Binding Proteins / Q000235:genetics*; D013960:Thyroid Function Tests; D014284:Triiodothyronine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D016601:RNA-Binding Proteins; C121530:SECISBP2 protein, human; D014284:Triiodothyronine; D019382:Human Growth Hormone