See Table A. Genes and Databases for chromosome locus and protein.

See Molecular Genetics for information on variants detected in this gene.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020]

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Gene-targeted deletion/duplication testing will detect deletions ranging from a single exon to the whole gene; however, breakpoints of large deletions and/or deletion of adjacent genes may not be detected by these methods. Exome and genome sequencing may be able to detect deletions/duplications using breakpoint detection or read depth; however, sensitivity can be lower than gene-targeted deletion/duplication analysis.

Partial and whole-gene deletions have been reported [Devos et al 2006, Teissier et al 2012, Invernizzi et al 2018].

Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including NKX2-1) that cannot be detected by sequence analysis. The ability to determine the size of the deletion/duplication depends on the type of microarray used and the density of probes in the 14q13.3 region.

Several large contiguous deletions have been identified in individuals with clinical features of NKX2-1-related disorders, including an individual with choreiform movements, neonatal respiratory distress, and hypothyroidism and a 3.5-Mb deletion adjacent to but not interrupting NKX2-1 [Barnett et al 2012]. A large 14q12-q21.1 deletion that included NKX2-1 was reported in a newborn with respiratory distress syndrome, hypothyroidism, and seizures [Villamil-Osorio et al 2021]. A deletion in a noncoding region downstream of NKX2-1 was also identified in three unrelated families with benign hereditary chorea [Liao et al 2021]. See Molecular Genetics.