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.

Consideration must be given to the sequence analysis of the TNXA pseudogene homolog region of TNXB; TNXB-specific primers may be designed and/or a long-range PCR assay performed. Two overall approaches exist: Sanger sequencing analysis of the entire gene or next-generation sequencing plus Sanger sequencing for the pseudogene homolog region.

Note that certain DNA variants characterize the recurrent TNXA/TNXB gene conversion events; namely, the c.12174C>G; p.Cys4058Trp (NM_019105​.8) and the 120-bp deletion (c.11435_11524+30del) variants (NG_008337​.2) together characterize TNXA/TNXB (CAH-X chimera 1), and c.12174C>G (p.Cys4058Trp) alone is characteristic of TNXA/TNXB (CAH-X chimera 2). Detection of these variants should trigger investigation for a likely gene conversion [Morissette et al 2015].

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 (e.g., those described by Chen et al [2016]) may not be detected by these methods. Smaller and larger deletions of TNXB have been reported in affected individuals [Demirdas et al 2017].

In 20%-30% of individuals with severe salt-wasting congenital adrenal hyperplasia (CAH), deletions of CYP21A2 are identified as a result of unequal crossover events during meiosis. These deletions are categorized into two subtypes: CAH and CAH-X. Three distinct CAH-X chimeras impair CYP21A2 and TNXB. Biallelic CAH-X leads to both CAH and TNXB-related clEDS.