title: Multiplex Ligation-dependent Probe Amplification improves the detection rate of NKX2.1 mutations in patients affected by brain-lung-thyroid syndrome.
abstract: BACKGROUND
  NKX2.1 mutations have been identified in patients displaying complete or partial brain-lung-thyroid syndrome, which can include benign hereditary chorea (BHC), hypothyroidism and/or lung disease.
  
  
  OBJECTIVE
  We evaluated the recently developed Multiplex Ligation-dependent Probe Amplification (MLPA) method to assess the relative copy number of genes. The goal was to determine if MLPA could improve, in addition to direct sequencing, the detection rate of NKX2.1 mutations in a phenotype-selected cohort of 24 patients affected by neurological, thyroid and/or pulmonary disorders.
  
  
  RESULTS
  Direct sequencing revealed two heterozygous mutations. Using MLPA, we identified two further heterozygous NKX2.1 gene deletions. MLPA increased the detection rate by 50%. All patients with gene deletions identified were affected by BHC and congenital hypothyroidism.
  
  
  CONCLUSIONS
  MLPA should be considered as a complementary tool in patients with partial or total brain-lung-thyroid syndrome when direct sequencing failed to identify NKX2.1 mutations. All patients with an NKX2.1 mutation had BHC and congenital hypothyroidism, emphasizing the high prevalence of these signs associated with defective NKX2.1 alleles.
authors.affiliation: INSERM U845, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Teissier
authors.forename: Loïc
authors.initials: L
authors.lastname: Guillot
authors.forename: Aurore
authors.initials: A
authors.lastname: Carré
authors.forename: Melina
authors.initials: M
authors.lastname: Morandini
authors.forename: Chantal
authors.initials: C
authors.lastname: Stuckens
authors.forename: Hubert
authors.initials: H
authors.lastname: Ythier
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Gabor
authors.initials: G
authors.lastname: Szinnai
authors.forename: Jacques
authors.initials: J
authors.lastname: de Blic
authors.forename: Annick
authors.initials: A
authors.lastname: Clement
authors.forename: Juliane
authors.initials: J
authors.lastname: Leger
authors.forename: Mireille
authors.initials: M
authors.lastname: Castanet
authors.forename: Ralph
authors.initials: R
authors.lastname: Epaud
authors.forename: Michel
authors.initials: M
authors.lastname: Polak
mesh_terms: D002648:Child; D002675:Child, Preschool; D002819:Chorea / Q000235:genetics*; D003409:Congenital Hypothyroidism / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007231:Infant, Newborn; D008171:Lung Diseases / Q000235:genetics*; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques / Q000379:methods; D013577:Syndrome; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors