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Holoprosencephaly-7 (Autosomal Dominant, Nonsyndromic) via the PTCH1 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
PTCH1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
10675PTCH181479 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


  • 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 that affects 1 in 16,000 live births (Muenke and Gropman GeneReviews, 2008) and approximately 1 in 200 spontaneous abortions (Orioli et al. Hum Genet. 109:1-6, 2001). HPE results from failure of the developing forebrain to divide into two hemispheres and ventricles that causes a continuum of structural brain malformations ranging from alobar HPE to semilobar HPE to lobar HPE. In addition to the structural brain abnormality, patients with HPE may exhibit variable craniofacial anomalies including cyclopia, ocular hypotelorism, structurally and positionally abnormal proboscis, bilateral cleft lip, anophthalmia or microophthalmia, absent nasal septum, flat nose, or single central incisor. Because incomplete penetrance is a feature of dominantly-inherited HPE, relatively normal facial appearance can be seen in individuals who have causative gene variants and affected first degree relatives. Developmental delay is a nearly constant clinical manifestation of HPE. Other findings include short stature, failure to thrive, seizures, feeding problems, and hypothalamic and brain stem dysfunction. Severely affected newborns with alobar HPE, cyclopia, and ethmocephaly usually do not live beyond the first week of life (Croen et al. Am J Med Genet 64:465-472, 1996) but survival is greater in those cases with less severe craniofacial anomalies (Barr and Cohen Am J Med Genet 89:116-120, 1999). More than half of all infants with semilobar or lobar HPE and no other major organ system involvement survive the first year of life (Olsen et al. Am J Med Genet 73:217-226, 1997; Barr and Cohen, 1999).


Holoprosencephaly has both genetic and non-genetic causes. The most common non-genetic cause is maternal diabetes, which confers a risk of 1% to infants of diabetic mothers (Barr et al. J Pediatr 102:565-568, 1983). Chromosome aneuploidy and structural abnormality is the overall single most common cause accounting for 25%-50% of all cases; while another 18%-25% of all cases occur as part of syndromes resulting from single gene variants (Muenke and Gropman GeneReviews, 2008). Both autosomal recessive and dominant syndromes with HPE as a feature are known. Nonsyndromic HPE is inherited as an autosomal dominant disorder with incomplete penetrance and intrafamilial variable expression. It is estimated that approximately one-third of obligate carriers of autosomal dominant forms of HPE are asymptomatic with normal cognitive function (Cohen Teratology 40:211-35, 1989). Seven loci, including five documented genes and one candidate gene (TMEM1), have been identified as causes of autosomal dominant nonsyndromic HPE. The five HPE genes are SHH, ZIC2, SIX3, TGIF1, and PTCH1. Another gene, GLI2, is associated with facial features typical of HPE but does not cause typical CNS findings. In addition to HPE, PTCH1 variants cause Gorlin syndrome and sporadic basal cell carcinoma (Bale and Yu Hum Mol Genet 10:757-762, 2001). All HPE7 cases have been found to harbor PTCH1 missense variants.

Clinical Sensitivity - Sequencing with CNV PG-Select

PTCH1 variants are a rare cause of HPE. Thus far, five unrelated individuals with HPE have been found to have PTCH1 variants (Ming et al. Hum Genet 110:297-301, 2002).

Testing Strategy

This test provides full coverage of all coding exons of the PTCH1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Individuals with clinical presentations in the HPE spectrum.


Official Gene Symbol OMIM ID
PTCH1 601309
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Holoprosencephaly 7 AD 610828

Related Tests

Autosomal Dominant, Non-Syndromic Holoprosencephaly via the GAS1 Gene
Holoprosencephaly-2 (Autosomal Dominant, Nonsyndromic) via the SIX3 Gene
Holoprosencephaly-3 (Autosomal Dominant Nonsyndromic) via the SHH Gene
Holoprosencephaly-4 (Autosomal Dominant, Nonsyndromic) via the TGIF1 Gene
Nevoid Basal Cell Carcinoma Syndrome/Gorlin Syndrome via the PTCH1 Gene


  • Bale, A. E., Yu, K. P. (2001). "The hedgehog pathway and basal cell carcinomas." Hum Mol Genet 10(7): 757-62. PubMed ID: 11257109
  • Bale, A. E., Yu, K. P. (2001). "The hedgehog pathway and basal cell carcinomas." Hum Mol Genet 10(7): 757-62. PubMed ID: 11257109
  • Barr, M., Jr., Cohen, M. M., Jr. (1999). "Holoprosencephaly survival and performance." Am J Med Genet 89(2): 116-20. PubMed ID: 10559767
  • Barr, M., Jr., et.al. (1983). "Holoprosencephaly in infants of diabetic mothers." J Pediatr 102(4): 565-8. PubMed ID: 6834191
  • Cohen, M. M., Jr. (1989). "Perspectives on holoprosencephaly: Part I. Epidemiology, genetics, and syndromology." Teratology 40(3): 211-35. PubMed ID: 2688166
  • Croen, L. A., et.al. (1996). "Holoprosencephaly: epidemiologic and clinical characteristics of a California population." Am J Med Genet 64(3): 465-72. PubMed ID: 8862623
  • Maximilian Muenke, Andrea Gropman (2008). "Holoprosencephaly Overview."
  • Maximilian Muenke, Andrea Gropman (2008). "Holoprosencephaly Overview."
  • Ming, J. E., et.al. (2002). "Mutations in PATCHED-1, the receptor for SONIC HEDGEHOG, are associated with holoprosencephaly." Hum Genet 110(4): 297-301. PubMed ID: 11941477
  • Olsen, C. L., et.al. (1997). "Epidemiology of holoprosencephaly and phenotypic characteristics of affected children: New York State, 1984-1989." Am J Med Genet 73(2): 217-26. PubMed ID: 9409876
  • 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


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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