title: Genetic analysis of the paired box transcription factor (PAX8) gene in a cohort of Polish patients with primary congenital hypothyroidism and dysgenetic thyroid glands.
abstract: BACKGROUND
  The morphological and biochemical phenotype of PAX8 mutation in patients with congenital hypothyroidism (CH) is variable. The contribution of mutations in PAX8 gene in children with CH and dysgenetic thyroid glands still remains a subject of interest for researchers.
  
  
  METHODS
  Some 48 children (37 girls and 11 boys) with CH associated with thyroid ectopy (n=22), agenesis (n=10), hypoplasia (n=6), or thyroid dysgenesis of unknown cause (n=10) were enrolled. The study participants were born in south-eastern Poland in the years 1993-2012 and were selected for neonatal mass screening for CH. DNA was extracted from peripheral blood samples using Master Pure DNA Purification Kit (Epicentre Biotechnologies, Madison, WI, USA). The 12 exons of the PAX8 gene along with their exon-intron boundaries were amplified and sequenced by the Sanger method. Capillary electrophoresis was run on ABI 3500 (Applied Biosystems, Carlsbad, CA, USA).
  
  
  RESULTS
  Novel heterozygous transition in exon 3 (c.68G>A) was detected in a 3-year-old girl with a thyroid hypoplasia. This substitution was not identified in the patient's parents (de novo event). Additionally, a novel genetic variant in 3'UTR region of exon 12 (c.*416C>T) occurred in a 3-year-old boy with ectopic thyroid tissue and concomitant congenital urogenital malformation. This heterozygous variant was also detected in other healthy family members. Thirteen well-described single nucleotide polymorphisms were revealed in the PAX8 gene.
  
  
  CONCLUSIONS
  The study reports on the occurrence of two novel heterozygous substitutions in the PAX8 gene. Estimation of the contribution of the revealed c.68G>A variant to the etiology of CH in a girl with hypoplastic thyroid requires further functional analysis.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kumorowicz-Czoch
authors.forename: Anna
authors.initials: A
authors.lastname: Madetko-Talowska
authors.forename: Adam
authors.initials: A
authors.lastname: Dudek
authors.forename: Dorota
authors.initials: D
authors.lastname: Tylek-Lemanska
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003409:Congenital Hypothyroidism / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011044:Poland / Q000453:epidemiology; D011379:Prognosis; D050033:Thyroid Dysgenesis / Q000453:epidemiology / Q000235:genetics*; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology*
chemical_list: D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors