title: Screening for Pax8 mutations in patients with congenital hypothyroidism in South-West Germany.
abstract: OBJECTIVE
  To study the frequency of mutations in the Pax8 gene in a cohort of patients with congenital hypothyroidism (CH) in South West Germany.
  
  
  METHODS
  A cohort of 95 patients with CH (60 females, 35 males), identified in our newborn screening program, was analyzed for mutations in Pax8 by single-stranded conformational polymorphism (SSCP) and DNA sequencing.
  
  
  RESULTS
  SSCP analysis and direct sequencing of exon 3 of a female patient with a hypoplastic thyroid gland revealed two heterozygous mutations in Pax8 resulting in a transition of T to C (codon 34) and G to A (codon 35), replacing isoleucine by threonine and valine by isoleucine. Using allele-specific PCR we could demonstrate that both mutations are located on the same allele. Furthermore, a polymorphism was documented in 24 patients with thyroid hypoplasia in intron 6 at nucleotide +51 (CC, GG, CG). Comparison of the polymorphisms between hypothyroid patients and controls revealed no significant differences suggesting that this polymorphism does not play a role in the pathogenesis of hypothyroidism. No further mutations or polymorphisms were found in the cohort.
  
  
  CONCLUSIONS
  These findings confirm the contribution of mutations in the Pax8 gene to the etiology of thyroid dysgenesis with a variable penetrance, but also demonstrate the rare overall incidence in CH.
authors.affiliation: Division of Pediatric Endocrinology and Diabetology, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Lanzerath
authors.forename: Markus
authors.initials: M
authors.lastname: Bettendorf
authors.forename: Christine
authors.initials: C
authors.lastname: Haag
authors.forename: Caroline
authors.initials: C
authors.lastname: Kneppo
authors.forename: Egbert
authors.initials: E
authors.lastname: Schulze
authors.forename: Jürgen
authors.initials: J
authors.lastname: Grulich-Henn
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003409:Congenital Hypothyroidism / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005860:Germany, West; D006801:Humans; D007231:Infant, Newborn; D007438:Introns; D008297:Male; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors