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.

Review of approximately 90 pathogenic variants in the published literature [Author, personal observation], correlation with smaller published case series [Jenkins et al 2009, Perdu et al 2011], and 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.

Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including AMER1) 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 Xq11.2 region. CMA designs in current clinical use target the Xq11.2 region.

Several contiguous deletions including AMER1 have been reported in individuals with features of OS-CS [Chénier et al 2012, Herman et al 2013, Holman et al 2013]. Contiguous gene deletions that include AMER1 and neighboring genes ARHGEF9 and MTMR8 appear to cause OS-CS with intellectual disability in females. Deletions including AMER1 and ASB12 only are not reported to be associated with intellectual disability [Holman et al 2013].