title: A Novel Mutation (S54C) of the PAX8 Gene in a Family with Congenital Hypothyroidism and a High Proportion of Affected Individuals.
abstract: BACKGROUND
  Congenital hypothyroidism (CH) is a common endocrine disorder in newborns. The cause of CH is thyroid dysgenesis in 80-85% of patients. Paired box gene 8 (PAX8) is a thyroid transcription factor that plays an important role in thyroid organogenesis and development. To date, 22 different PAX8 gene mutations have been reported.
  
  
  METHODS
  Four generations of a Hungarian Jewish family were affected, and in the 3 generations studied, 9 males and 4 females were affected and 3 first-degree relatives were unaffected. Six were diagnosed at birth [thyroid-stimulating hormone (TSH) level 59-442 mU/l] and 7 at 2-48 years of age (TSH level 6-223 mU/l). One affected patient had thyroid hemiagenesis on ultrasound.
  
  
  RESULTS
  Direct sequencing of the PAX8 gene revealed a novel single nucleotide substitution (c.162 A>T) in exon 2 that resulted in the substitution of the normal serine 54 with a cysteine (S54C), which segregated with elevated serum TSH levels. Other mutations of the same amino acid (S54G and S54R) have also been shown to produce functional impairment.
  
  
  CONCLUSIONS
  We report a large family with a novel mutation in the PAX8 gene presenting with variable phenotype and with a high proportion of affected family members.
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, Ill., USA.
authors.forename: Panudda
authors.initials: P
authors.lastname: Srichomkwun
authors.forename: Osnat
authors.initials: O
authors.lastname: Admoni
authors.forename: Samuel
authors.initials: S
authors.lastname: Refetoff
authors.forename: Liat
authors.initials: L
authors.lastname: de Vries
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D044903:Congenital Hyperinsulinism / Q000097:blood / Q000235:genetics*; D005190:Family; D005260:Female; D006801:Humans; D006814:Hungary; D007585:Jews; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D000072636:PAX8 Transcription Factor / Q000235:genetics*; D013972:Thyrotropin / Q000097:blood
chemical_list: D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D013972:Thyrotropin