title: A novel deletion in the thyrotropin Beta-subunit gene identified by array comparative genomic hybridization analysis causes central congenital hypothyroidism in a boy originating from Turkey.
abstract: BACKGROUND
  Isolated central congenital hypothyroidism (ICCH) is rare but important. Most ICCH patients are diagnosed later, which results in severe growth failure and intellectual disability.
  
  
  OBJECTIVE
  We describe a boy with ICCH due to a large homozygous TSHβ gene deletion.
  
  
  RESULTS
  A 51-day-old male Turkish infant, whose parents were first cousins, was admitted for evaluation of prolonged jaundice. His clinical appearance was compatible with hypothyroidism. Venous thyrotropin (TSH) was undetectably low, with a subsequent low free T4 and a low free T3, suggestive of central hypothyroidism. Using different PCR protocols, we could not amplify both coding exons of the boy's TSHβ gene, which suggested a deletion. An array comparative genomic hybridization (aCGH) using specific probes around the TSHβ gene locus showed him to be homozygous for a 6-kb deletion spanning all exons and parts of the 5' untranslated region of the gene.
  
  
  CONCLUSIONS
  Infants who are clinically suspected of having hypothyroidism should be evaluated thoroughly, even if their TSH-based screening result is normal. In cases with ICCH and undetectably low TSH serum concentrations, a TSHβ gene deletion should be considered; aCGH should be performed when gene deletions are suspected. In such cases, PCR-based sequencing techniques give negative results.
authors.affiliation: Department of Pediatrics, Johannes Gutenberg University Medical School, Mainz, Germany.
authors.forename: Pia
authors.initials: P
authors.lastname: Hermanns
authors.forename: Robert
authors.initials: R
authors.lastname: Couch
authors.forename: Norma
authors.initials: N
authors.lastname: Leonard
authors.forename: Cherise
authors.initials: C
authors.lastname: Klotz
authors.forename: Joachim
authors.initials: J
authors.lastname: Pohlenz
mesh_terms: D004247:DNA / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics*; D007223:Infant; D008297:Male; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D013972:Thyrotropin / Q000097:blood; D037322:Thyrotropin, beta Subunit / Q000235:genetics*; D013974:Thyroxine / Q000097:blood; D014421:Turkey
chemical_list: D037322:Thyrotropin, beta Subunit; D013972:Thyrotropin; D004247:DNA; D013974:Thyroxine