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], Pop et al [2004], and von Bohlen et al [2017]

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., the family described by Castori et al [2016]) may not be detected by these methods.

SOX9 duplication causes XX sex reversal only.

Olney et al [1999], Pop et al [2004], Smyk et al [2007]

Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including SOX9) 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 17q24.3 region. CMA designs in current clinical use target the 17q24.3 region.

Deletions of SOX9 or upstream regulatory regions cause campomelic dysplasia [Pop et al 2004, Lecointre et al 2009, Kayhan et al 2019].

There are multiple reports of individuals with campomelic dysplasia (including the acampomelic form) due to apparently balanced translocations in the vicinity of the SOX9 locus (breakpoint may be 1 Mb distant, either upstream or downstream) [Ninomiya et al 1995, Pfeifer et al 1999, Fonseca et al 2013, Walters-Sen et al 2014]. Of note, array CGH in at least two of these cases did not detect any imbalance [Fonseca et al 2013].