Benign hereditary chorea and deletions outside NKX2-1: What's the role of MBIP?

Eur J Med Genet. 2018 Oct;61(10):581-584. doi: 10.1016/j.ejmg.2018.03.011. Epub 2018 Apr 3.


Heterozygous point mutations or deletions of the NKX2-1 gene cause benign hereditary chorea (BHC) or a various combinations of primary hypothyroidism, respiratory distress and neurological disorders. Deletions proximal to, but not encompassing, NKX2-1 have been described in few subjects with brain-lung-thyroid syndrome. We report on a three-generation Italian family, with 6 subjects presenting BHC and harboring a genomic deletion adjacent to NKX2-1 and including the gene MBIP, recently proposed to be relevant for the pathogenesis of brain-lung-thyroid syndrome. We observed a clear reduction of NKX2-1 transcript levels in fibroblasts from our patients compared to controls; this finding suggests that MBIP deletion affects NKX2-1 expression, mimicking haploinsufficiency caused by classical NKX2-1 related mutations.

Keywords: Benign hereditary chorea; Brain-lung-thyroid syndrome; MBIP; NKX2-1.

MeSH terms

  • Cells, Cultured
  • Chorea / genetics*
  • Haploinsufficiency
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Pedigree
  • Sequence Deletion*
  • Thyroid Nuclear Factor 1 / genetics*
  • Thyroid Nuclear Factor 1 / metabolism


  • Intracellular Signaling Peptides and Proteins
  • MBIP protein, human
  • NKX2-1 protein, human
  • Thyroid Nuclear Factor 1