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.
AIMS AND METHODS: 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.
CONCLUSION: 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.