GLI3-Related Disorders via the GLI3 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
8103 GLI3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8103GLI381479 81479 $890 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.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

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


Genetic Counselors


Clinical Features and Genetics

Clinical Features

Greig Cephalopolysyndactyly Syndrome (GCPS) is a clinically heterogeneous disorder that is characterized by craniofacial and digital malformations. The clinical diagnosis of GCPS is based on the presence of preaxial polydactyly, syndactyly, macrocephaly, and ocular hypertelorism (Johnston et al. Hum Mutat 31:1142-54, 2010). Additional features include prominent forehead, seizures, hydrocephalus, developmental delay, learning difficulties and postaxial polydactyly. For more information see Biesecker GeneReviews 2009 (

Pallister-Hall Syndrome (PHS) characterized by postaxial polydactyly and hypothalamic hamartoma (Johnston, 2010). Additional features include gelastic seizures, small nails, imperforate anus, bifid epiglottis and laryngotracheal clefts. PHS patients may have pituitary insufficiency which can result in death from adrenal insufficiency. Symptoms are variable in appearance and severity. Inter-familial variability has been reported to be much greater than intra-familial variability. For more information see Biesecker GeneReviews 2012 (

Nonsyndromic polydactyly, including preaxial and postaxial, is characterized by abnormalities in the digits of the hands or feet with no other symptoms or abnormalities that are usually present in GCPS or PHS (Radhakrishna et al. Nat Genet 17:269–71, 1997; Radhakrishna et al. Am J Hum Genet 65:645–55, 1999).


GCPS is an autosomal dominant disorder that is caused by loss of function mutations in the GLI3 gene (Vortkamp et al. Nature 352:539-40; 1991; Kalff-Suske et al. Hum Mol Genet 8:1769-77, 1999; Johnston et al. Am J Hum Genet 76: 609-22, 2005). Mutations occur either de novo or are inherited dominantly. The fraction of patients with de novo mutations is unknown. GLI3 is the only gene that has been implicated in GCPS. Causative mutations are located throughout the length of the gene, but especially within the first and last thirds of the gene (Johnston et al. 2005; Johnston, 2010). About 5-10% of GCPS patients have large deletions or translocations involving the GLI3 gene (Johnston et al. Am J Med Genet A 123:236-42, 2003; Biesecker 2009).

PHS is an autosomal dominant disorder that is caused by mutations in the GLI3 gene. These mutations result in a constitutive repressor protein leading to a loss of balance between the activator and repressor forms of the GLI3 protein, which is critical for Sonic Hedgehog (SHH) signaling (Kang et al. Nat Genet 15:266-8, 1997; Johnston, 2005). Mutations either occur de novo or are inherited dominantly. De novo mutations occur in ~ 25 % of patients and are usually associated in a more severe phenotype compared to that of familial cases (Biesecker, 2012). PHS mutations are mostly (possibly even entirely) truncating (nonsense, frameshift, and obvious splicing defects) and are usually located within the middle third of the gene (Johnston, 2005). No large deletions or complex rearrangements have been reported to date. GLI3 is the only gene that has been implicated in PHS.

In addition to GCPS and PHS, heterozygous mutations in the GLI3 gene cause nonsyndromic polydactyly (Radhakrishna 1997; Radhakrishna 1999). GLI3 encodes a zinc finger protein of the GLI family, which has a double role. The GLI3 protein acts as a DNA-binding transcription factor and as a mediator of SHH signaling, which is involved in the regulation of vertebrate organogenesis.

Clinical Sensitivity - Sequencing with CNV PGxome

This test will detect causative mutations in about 70% of GCPS patients (Biesecker 2009), and about 95% of PSH patients (Biesecker 2012).

Testing Strategy

This test provides full coverage of all coding exons of the GLI3 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Patients with symptoms consistent with GCPS, PHS or nonsyndromic polydactyly are candidates for this test.


Official Gene Symbol OMIM ID
GLI3 165240
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


  • Johnston et al. (2003). "Clinical and molecular delineation of the Greig cephalopolysyndactyly contiguous gene deletion syndrome and its distinction from acrocallosal syndrome." Am J Med Genet A 123A(3): 236-42. PubMed ID: 14608643
  • Johnston et al. (2010). "Molecular analysis expands the spectrum of phenotypes associated with GLI3 mutations." Hum Mutat 31: 1142-54. PubMed ID: 20672375
  • Johnston (2005). "Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: robust phenotype prediction from the type and position of GLI3 mutations." Am J Hum Genet 76(4): 609-22. PubMed ID: 15739154
  • Kalff-Suske (1999). "Point mutations throughout the GLI3 gene cause Greig cephalopolysyndactyly syndrome." Hum Mol Genet 8: 1769-77. PubMed ID: 10441342
  • Kang al. (1997). "GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome." Nat Genet 15(3): 266-8. PubMed ID: 9054938
  • Leslie G Biesecker. "Greig Cephalopolysyndactyly Syndrome." GeneReviews, 2009. PubMed ID: 20301619
  • Leslie G Biesecker. "Pallister-Hall Syndrome." GeneReviews, 2012. PubMed ID: 20301638
  • Radhakrishna et al. (1997). "Mutation in GLI3 in postaxial polydactyly type A. Nat Genet 17:269–71". PubMed ID: 9354785
  • Radhakrishna et al. (1999). "The phenotypic spectrum of GLI3 morphopathies includes autosomal dominant preaxial polydactyly type-IV and postaxial polydactyly type-A/B; no phenotype prediction from the position of GLI3 mutations". Am J Hum Genet 65:645–55. PubMed ID: 10441570
  • Vortkamp et al. (1991).  "GLI3 zinc-finger gene interrupted by translocations in Greig syndrome families." Nature 352:539-40. PubMed ID: 1650914


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.

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

Specimen Types

Specimen Requirements and Shipping Details

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View Ordering Instructions

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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