title: Thyrotropin-stimulating hormone receptor gene analysis in pediatric patients with non-autoimmune subclinical hypothyroidism.
abstract: BACKGROUND
  Mutations in TSH receptor (TSHR) are notoriously associated with congenital hypothyroidism as well as with non-autoimmune subclinical hypothyroidism, a mild form of TSH resistance that is not as well characterized by diagnostic procedures.
  
  
  OBJECTIVE
  The genetic analysis of the TSHR gene was performed to determine the prevalence of TSHR gene mutations in non-autoimmune subclinical hypothyroidism during the pediatric age. The new mutations were studied for genotypic-phenotypic correlation.
  
  
  METHODS
  Thirty-eight children (ages 0.5-18.0 yr) affected by non-autoimmune subclinical hypothyroidism diagnosed in our center (follow-up from 1 to 11.5 yr) and normal at neonatal screening were enrolled in the genetic study. In 11 cases, the relatives were included in the genetic analysis.
  
  
  RESULTS
  Eleven different mutations of the TSHR gene were identified in 11 of the 38 patients. Two are new: the nonsense mutation C31X and the missense mutation P68S, which shows a decrease in TSH binding capacity but not in biological activity. In all cases the carrier parent was identified.
  
  
  CONCLUSIONS
  To date, this study demonstrates the highest prevalence (29%) of TSHR gene mutations in children and adolescents with non-autoimmune subclinical hypothyroidism not selected by neonatal screening. Functional studies show that some mutations cause a slight inactivation of the TSHR. This reveals a possible limit of the in vitro study or of the knowledge of mechanisms involving TSHR, or that other candidate genes must be considered.
authors.affiliation: Department of Gynaecologic, Obstetric, and Paediatric Sciences, S Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Nicoletti
authors.forename: Milva
authors.initials: M
authors.lastname: Bal
authors.forename: Giuseppina
authors.initials: G
authors.lastname: De Marco
authors.forename: Lilia
authors.initials: L
authors.lastname: Baldazzi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Agretti
authors.forename: Soara
authors.initials: S
authors.lastname: Menabò
authors.forename: Elisa
authors.initials: E
authors.lastname: Ballarini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cicognani
authors.forename: Massimo
authors.initials: M
authors.lastname: Tonacchera
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cassio
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D000818:Animals; D019556:COS Cells / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D005190:Family; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics*; D007223:Infant; D009154:Mutation; D011989:Receptors, Thyrotropin / Q000235:genetics*; D013972:Thyrotropin / Q000097:blood / Q000378:metabolism; D014162:Transfection
chemical_list: D011989:Receptors, Thyrotropin; D013972:Thyrotropin