14q13 deletion, the NKX2-1 gene and BHC

Chromosome 14 ideogram

Chromosome 14q13 deletion, NKX2-1 deletion or mutation and BNC. The chromosomal segment 14q13 includes several genes, including the NKX2-1 gene. Deletions or mutations of this gene cause benign hereditary chorea (BHC). Manifestations of this disorder, which occurs in childhood, include non-progressive choreic movement, usually without cognitive decline. There are numerous reports of BHC with different mutations of the NKX2-1 gene or different deletions involving this gene. However, in recent years there are several reports of BHC patients who did not have either a deletion or mutation of NKX2-1. The authors report on 3 families with inherited BHC (a total of 11 affected patients). Although there are no direct relations between these families, all affected patients were found having a 117 kb deletion in 14q13 downstream of the NKX2-1 gene. Other healthy family members did not have this deletion. The identical deletion indicates the founder effect (most likely the deletion occurred in a common ancestor for all 3 families). The authors also reported on a sporadic patient with BHC who had a 648 kb deletion in 14q13, also downstream of NKX2-1. The comparison with previously reported cases of BHC with deletions outside the NKX2-1 gene, showed a small region of overlap in a tiny 33 kb segment which does not include any genes, but includes multiple evolutionarily conserved non-coding sequences. Most likely this area includes regulatory elements necessary for NKX2-1 expression. In genetic terms, deletions of regulatory elements (enhancers or silencers) may produce clinical manifestations even if the functional gene itself remains intact.

Liao J. et al. Deletion of conserved non-coding sequences downstream from NKX2-1: a novel disease-causing mechanism for benign hereditary chorea. “Molec. Genet. Genomic Med.” 2021, v. xx (x), xx-xx.

Newly published articles are selected for inclusion on the CDO research pages by Dr. Iosif Lurie, M.D. Ph.D. CDO Medical Advisor. For more information on any article please contact info@chromodisorder.org