title: A novel NKX2.1 mutation in a family with hypothyroidism and benign hereditary chorea.
abstract: BACKGROUND
  We studied a boy with congenital hypothyroidism, benign hereditary chorea, and respiratory distress. His mother and his grandfather were affected by hypothyroidism with a late onset and benign hereditary chorea. The aim of this study was to establish the genetic defects that cause that phenotype and study the molecular mechanisms of the pathology.
  
  
  METHODS
  NKX2.1, PAX8, NKX2.5, and TAZ genes were sequenced.
  
  
  RESULTS
  Direct sequencing of the NKX2.1 gene showed, in all the affected, a new heterozygous mutation from cytosine to adenine in the second base of the triplet encoding for the amino acid at position 145. The mutation (C609A) is responsible for a change from serine to a stop codon (S145X). We also demonstrated that the mutant protein is predominantly in the cytoplasm and unable to translocate into the nucleus. Of note, the S145X mutation produces variable phenotypes in the affected members of the family. No mutations have been identified in the NKX2.5, PAX8, and TAZ genes.
  
  
  CONCLUSIONS
  Our study extends the knowledge of the functional effect of NKX2.1 mutations and further highlights the complexities of genotype-phenotype correlation in the NKX2.1 deficiency syndromes.
authors.affiliation: Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università degli Studi di Napoli Federico II, Napoli, Italy.
authors.forename: Alfonso Massimiliano
authors.initials: AM
authors.lastname: Ferrara
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Michele
authors.forename: Elena
authors.initials: E
authors.lastname: Salvatore
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Maio
authors.forename: Emilia
authors.initials: E
authors.lastname: Zampella
authors.forename: Serena
authors.initials: S
authors.lastname: Capuano
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Del Prete
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Rossi
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Fenzi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Filla
authors.forename: Paolo Emidio
authors.initials: PE
authors.lastname: Macchia
mesh_terms: D002819:Chorea / Q000235:genetics*; D005192:Family Health; D005260:Female; D006579:Heterozygote; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D012120:Respiration Disorders / Q000235:genetics; D017422:Sequence Analysis, DNA; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors