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Microform Holoprosencephaly (HPE10) via the DISP1 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
DISP1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11231DISP181479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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


  • Stela Berisha, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Holoprosencephaly (HPE, OMIM 236100) is a common developmental anomaly of the human forebrain and midface affecting 1 in 16,000 live births (Solomon et al. GeneReviews, 2008) and approximately 1 in 200 spontaneous abortions (Orioli et al. 2001. PubMed ID: 11479728). Disruption of the sonic hedgehog (SHH) signaling pathway, and specifically variants of the SHH ligand encoded by the SHH gene, is the most common underlying cause of HPE (Roessler et al. 2009. PubMed ID: 19603532). Other proteins involved with the SHH pathway are also known to be involved in the HPE spectrum. Those proteins include the receptor of the SHH ligand, encoded by the PTCH1 gene; the GLI2 gene product, which is involved in transduction of SHH ligand; and the SIX3 gene product, which acts as a regulator of SHH gene transcription. Another protein, termed "homolog of Drosophila dispatched 1’" is encoded by the DISP1 gene (OMIM 607502), and is required for secretion of SHH ligand. Experimental evidence indicates that DISP1-mediated release of soluble SHH ligand is negatively affected by alteration in functionally important residues of the PTCH1 gene product (Ma et al. 2002. PubMed ID: 12372301). Consequently, DISP1 was considered an HPE candidate gene because of its functional role in SHH signaling and its location at chromosome 1q41 where the HPE10 locus (OMIM 612530) was previously mapped (Roessler and Muenke. 1998. PubMed ID: 9728329). In a study of a large HPE cohort consisting of patients with mild to severe clinical presentations,  two unrelated children with microform HPE and truncating variants of the DISP1 gene were found (Roessler et al. 2009. PubMed ID: 19184110). One child had a history of seizures, developmental delay including speech, and cleftlip/palate. She was diagnosed as having HPE sequence with a normal head CT scan. The second case had clear signs of microform HPE with a repaired bilateral cleft-lip/palate, hypotelorism, upslanting palpebral fissures, and a solitary maxillary central incisor. She was of normal intelligence and had a normal brain MRI. Previously, (Shaffer et al. 2007. PubMed ID: 17873649) reported seven de novo cases of chromosome 1q41-q42 deletion syndrome with features of developmental delay, seizures, craniofacial dysmorphisms, microcephaly, cleft palate, clubfeet, and short stature. As a result of the phenotypic similarity of these seven patients to the two cases described above, and because DISP1 is located within the 1q41-q42 region, Roessler et al. suggested that haploinsufficiency for DISP1 may confer susceptibility to the craniofacial and neurodevelopmental disorders at the mild end of the HPE spectrum (Roessler et al. 2009. PubMed ID: 19184110).


The two reported DISP1 variants predict heterozygous loss of function, and both were inherited from a clinically unaffected parent. Roessler et al. commented that incomplete penetrance is not inconsistent with microforms of HPE (Roessler et al. 2009. PubMed ID: 19184110).

The DISP1 gene is composed of 7 coding exons and is located on chromosome 1q41.

Clinical Sensitivity - Sequencing with CNV PGxome

Two cases with DISP1 variants were found among a cohort of 520 HPE patients (Roessler et al. 2009. PubMed ID: 19184110).

Testing Strategy

This test provides full coverage of all coding exons of the DISP1 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Patients with microform HPE.


Official Gene Symbol OMIM ID
DISP1 607502
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Holoprosencephaly Sequence 236100


  • Benjamin D Solomon, et.al. (2011). "Holoprosencephaly Overview." PubMed ID: 20301702
  • Ma, Y., et.al. (2002). "Hedgehog-mediated patterning of the mammalian embryo requires transporter-like function of dispatched." Cell 111(1): 63-75. PubMed ID: 12372301
  • Orioli, I. M., et.al. (2001). "Identification of novel mutations in SHH and ZIC2 in a South American (ECLAMC) population with holoprosencephaly." Hum Genet 109(1): 1-6. PubMed ID: 11479728
  • Roessler, E., et.al. (2009). "The mutational spectrum of holoprosencephaly-associated changes within the SHH gene in humans predicts loss-of-function through either key structural alterations of the ligand or its altered synthesis." Hum Mutat 30(10): E921-35. PubMed ID: 19603532
  • Roessler, E., et.al. (2009). "Truncating loss-of-function mutations of DISP1 contribute to holoprosencephaly-like microform features in humans." Hum Genet 125(4): 393-400. PubMed ID: 19184110
  • Roessler, E., Muenke, M. (1998). "Holoprosencephaly: a paradigm for the complex genetics of brain development." J Inherit Metab Dis 21(5): 481-97. PubMed ID: 9728329
  • Shaffer, L. G., et.al. (2007). "The discovery of microdeletion syndromes in the post-genomic era: review of the methodology and characterization of a new 1q41q42 microdeletion syndrome." Genet Med 9(9): 607-16. PubMed ID: 17873649


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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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