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

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

A chromosomal microarray (CMA) that includes probe coverage of EHMT1 can detect deletions of 9q34.3 (de novo terminal deletions, complex rearrangements or derivative chromosomes, interstitial deletion).

CMA testing is appropriate to define breakpoints of large deletions; however, intragenic deletions in EHMT1 may not be detected by this method.

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.

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 methods will detect single-exon up to whole-gene deletions; however, breakpoints of large deletions and/or deletion of adjacent genes may not be determined. Gene-targeted deletion/duplication analysis of EHMT1 may detect an additional ~5% of affected individuals who have had a normal chromosomal microarray, but this is highly dependent on the resolution and probe coverage of the array platform that was used for analysis.

Routine karyotype will not detect the 9q34.3 deletion. Karyotype may be considered in those with features of Kleefstra syndrome in whom a pathogenic variant (mutation or deletion) of EHMT1 has not been identified using other methods (e.g., CMA, sequence analysis). Karyotype can detect balanced chromosomal rearrangements that disrupt EHMT1.