title: Thyroid dyshormonogenesis is mainly caused by TPO mutations in consanguineous community.
abstract: OBJECTIVE
  In this study, we aimed to investigate the genetic background of thyroid dyshormonogenesis (TDH).
  
  
  BACKGROUND
  Thyroid dyshormonogenesis comprises 10-15% of all cases of congenital hypothyroidism (CH), which is the most common neonatal endocrine disorder, and might result from disruptions at any stage of thyroid hormone biosynthesis. Currently seven genes (NIS, TPO, PDS, TG, IYD, DUOX2 and DUOXA2) have been implicated in the aetiology of the disease.
  
  
  METHODS
  As TDH is mostly inherited in an autosomal recessive manner, we planned to conduct the study in consanguineous/multi-case families.
  
  
  METHODS
  One hundred and four patients with congenital TDH all coming from consanguineous and/or multi-case families.
  
  
  METHODS
  Initially, we performed potential linkage analysis of cases to all seven causative-TDH loci as well as direct sequencing of the TPO gene in cases we could not exclude linkage to this locus. In addition, in silico analyses of novel missense mutations were carried out.
  
  
  RESULTS
  TPO had the highest potential for linkage and we identified 21 TPO mutations in 28 TDH cases showing potential linkage to this locus. Four of 10 distinct TPO mutations detected in this study were novel (A5T, Y55X, E596X, D633N).
  
  
  CONCLUSIONS
  This study underlines the importance of molecular genetic studies in diagnosis, classification and prognosis of CH and proposes a comprehensive mutation screening by new sequencing technology in all newly diagnosed primary CH cases.
authors.affiliation: Department of Medical Genetics, Bahcesehir University School of Medicine, Istanbul, Turkey. h.cangul@bham.ac.uk
authors.forename: Hakan
authors.initials: H
authors.lastname: Cangul
authors.forename: Zehra
authors.initials: Z
authors.lastname: Aycan
authors.forename: Alvaro
authors.initials: A
authors.lastname: Olivera-Nappa
authors.forename: Halil
authors.initials: H
authors.lastname: Saglam
authors.forename: Nadia A
authors.initials: NA
authors.lastname: Schoenmakers
authors.forename: Kristien
authors.initials: K
authors.lastname: Boelaert
authors.forename: Semra
authors.initials: S
authors.lastname: Cetinkaya
authors.forename: Omer
authors.initials: O
authors.lastname: Tarim
authors.forename: Ece
authors.initials: E
authors.lastname: Bober
authors.forename: Feyza
authors.initials: F
authors.lastname: Darendeliler
authors.forename: Veysel
authors.initials: V
authors.lastname: Bas
authors.forename: Korcan
authors.initials: K
authors.lastname: Demir
authors.forename: Banu K
authors.initials: BK
authors.lastname: Aydin
authors.forename: Michaela
authors.initials: M
authors.lastname: Kendall
authors.forename: Trevor
authors.initials: T
authors.lastname: Cole
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Högler
authors.forename: V Krishna K
authors.initials: VK
authors.lastname: Chatterjee
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Barrett
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003409:Congenital Hypothyroidism / Q000235:genetics*; D003241:Consanguinity; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007453:Iodide Peroxidase / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010154:Pakistan; D013963:Thyroid Hormones / Q000096:biosynthesis / Q000235:genetics; D014421:Turkey
chemical_list: D013963:Thyroid Hormones; D007453:Iodide Peroxidase