title: One Base Deletion (c.2422delT) in the TPO Gene Causes Severe Congenital Hypothyroidism.
abstract: OBJECTIVE
  Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and mutations in the TPO gene have been reported to cause CH. Our aim in this study was to determine the genetic basis of CH in two affected individuals coming from a consanguineous family.
  
  
  METHODS
  Since CH is usually inherited in autosomal recessive manner in consanguineous/multi-case families, we adopted a two-stage strategy of genetic linkage studies and targeted sequencing of the candidate genes. First, we investigated the potential genetic linkage of the family to any known CH locus using microsatellite markers and then screened for mutations in linked-gene by Sanger sequencing.
  
  
  RESULTS
  The family showed potential linkage to the TPO gene and we detected a deletion (c.2422delT) in both cases. The mutation segregated with disease status in the family.
  
  
  CONCLUSIONS
  This study demonstrates that a single base deletion in the carboxyl-terminal coding region of the TPO gene could cause CH and helps to establish a genotype/phenotype correlation associated with the mutation. The study also highlights the importance of molecular genetic studies in the definitive diagnosis and accurate classification of CH.
authors.affiliation: Bahçeşehir University Faculty of Medicine, Department of Medical Genetics, İstanbul, Turkey. E-ma-il: h.cangul@bham.ac.uk.
authors.forename: Hakan
authors.initials: H
authors.lastname: Cangül
authors.forename: Murat
authors.initials: M
authors.lastname: Doğan
authors.forename: Yaman
authors.initials: Y
authors.lastname: Sağlam
authors.forename: Michaela
authors.initials: M
authors.lastname: Kendall
authors.forename: Kristien
authors.initials: K
authors.lastname: Boelaert
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Barrett
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
mesh_terms: D001324:Autoantigens / Q000235:genetics*; D002648:Child; D003409:Congenital Hypothyroidism / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D040941:Heredity; D006720:Homozygote; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics*; D033862:Iron-Binding Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012307:Risk Factors; D012720:Severity of Illness Index; D035781:Siblings
chemical_list: D001324:Autoantigens; D033862:Iron-Binding Proteins; C056658:TPO protein, human; D007453:Iodide Peroxidase