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Kleefstra Syndrome via the EHMT1 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
EHMT1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9847EHMT181479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Li Fan, MD, PhD, FCCMG, FACMG

Clinical Features and Genetics

Clinical Features

Kleefstra syndrome (KS; OMIM:610253), formerly 9q subetelomeric deletion syndrome (9qSTD), is a cognitive disorder characterized by moderate to severe intellectual disability, childhood hypotonia and distinct facial features. Craniofacial features commonly seen in KS patients include: a flat face with hypertelorism, upslanting palpebral fissures, brachycephaly, tented upper lip with an everted lower lip and prognathism (Kleefstra et al. Am J Hu Genet 79(2):370-377, 2006). Aggression and behavioral problems in KS patients often have adolescent or adult onset. Variable features of KS that are seen in a subset of patients include seizures, hearing loss, cardiac anomaly, male genital defects, obesity and synophrys (Willemsen et al. Mol Syndromol 2(3-5):202-212, 2011).


Kleefstra syndrome is caused by dominant loss-of-function mutations in or deletions of the EHMT1 gene. Nearly all cases of KS are sporadic, resulting from de novo mutations. KS phenotypes are similar in patients with point mutations in the EHMT1 gene and those with subtelomeric deletions of chromosome 9 (Kleefstra et al., 2006). The severity of the disease generally prevents inheritance of KS. A rare case of autosomal dominant inheritance of KS was reported where the parent was found to be mosaic for an EHMT1 mutation (Rump et al. Eu J Hu Genet 21(8):887-890, 2013). Mutations in EHMT1 are found in ~25% of KS cases (Kleefstra et al. Am J Hu Genet 91(1):73-82, 2012). Patients with gross duplications of 9q34.3 that include the EHMT1 gene have been reported to have learning disabilities and speech problems, suggesting that EHMT1 overexpression is also detrimental to cognitive development (Yatsenko et al. Hum Genet 131(12):1895-1910, 2012).

EHMT1 encodes the histone methyltransferase EHMT1. Histones contain amino acid ‘tails’ which can be modified in a variety of ways. Histone tail modifications regulate chromatin structure and influence which regions of the genome are transcribed. EHMT1 is a putative histone 3 lysine 9 (H3K9) methyltransferase. Methylation of histone 3 lysine 9 leads to transcriptional repression. It is hypothesized that misexpression of EHMT1 target genes, due to loss of histone methylation, underlies the KS phenotype in patients with EHMT1 mutations (Kleefstra et al., 2012).

Clinical Sensitivity - Sequencing with CNV PG-Select

In one study, EHMT1 mutations were found in 25% of patients who displayed core features of Kleefstra syndrome (Kleefstra et al. Am J Hu Genet 91(1):73-82, 2012).

Approximately 50% of EHMT1 variants reported in KS cases are large deletions (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the EHMT1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for EHMT1 testing are patients who display the core features of KS: moderate to severe intellectual disability, childhood hypotonia and characteristic facial features. Due to overlapping clinical features, patients diagnosed with Down syndrome, but with no evidence of Trisomy 21 and patients diagnosed with Smith-Magenis syndrome (SMS) who lack the 17p11.2 deletion might be good candidates for EHMT1 testing (Kleefstra et al., 2006). Carrier testing is recommended in parents of a child with KS to rule out the possibility of germline mosaicism (Rump et al., 2013).


Official Gene Symbol OMIM ID
EHMT1 607001
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Chromosome 9Q Deletion Syndrome AD 610253


  • Human Gene Mutation Database (Bio-base).
  • Kleefstra, T. et al. (2006). "Loss-of-Function Mutations in Euchromatin Histone Methyl Transferase 1 (EHMT1) Cause the 9q34 Subtelomeric Deletion Syndrome." Am J Hu Genet 79(2):370-377. PubMed ID: 16826528
  • Kleefstra, T. et al. (2012). "Disruption of an EHMT1-Associated Chromatin-Modification Moduce Causes Intellectual Disability." Am J Hu Genet 91(1):73-82. PubMed ID: 22726846
  • Rump, A. et al. (2013). "A mosaic maternal splice donor mutaiton in the EHMT1 gene leads to aberrant transcripts and to Kleefstra syndrome in the offspring." Eu J Hu Genet 21(8):887-890. PubMed ID: 23232695
  • Willemsen, M. H. et al. (2011). "Update on Kleefstra Syndrome." Mol Syndromol 2(3-5):202-212. PubMed ID: 22670141
  • Yatsenko, S.A. et al. (2012). “Human subtelomeric copy number gains suggest a DNA replication mechanism for formation: beyond breakage-fusion-bridge for telomere stabilization.” Hum Genet 131(12):1895-1910. PubMed ID: 22890305


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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