Ordering Recommendation

Appropriate first-tier test to confirm a clinical diagnosis of Pallister-Hall syndrome or Greig cephalopolysyndactyly syndrome.

Mnemonic
GLI3 FGS
Methodology

Polymerase Chain Reaction/Sequencing

Performed

Sun- Sat

Reported

14-21 days

New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.
Specimen Required
Patient Preparation
Collect

Lavender (EDTA), pink (K2EDTA), or Yellow (ACD Solution A or B).

Specimen Preparation

Transport 3 mL whole blood. (Min: 1 mL)

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions
Remarks
Stability

Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable

Reference Interval
Interpretive Data

Background Information for GLI3-Related Disorders (GLI3) Sequencing:
Characteristics
: Mutations in the GLI3 gene cause multiple disorders. The most common disorders are Pallister-Hall syndrome (PHS) and Greig Cephalopolysyndactyly syndrome (GCPS).
PHS
is characterized by hypothalamic hamartoma, postaxial/central polydactyly, and bifid epiglottis. Some individuals may exhibit imperforate anus, renal, genitourinary, pulmonary, or non-polydactyly skeletal anomalies.
GCPS
is characterized by preaxial polysyndactyly, hypertelorism, and macrocephaly. Severe cases may exhibit seizures, hydrocephalus, and/or intellectual disability.
Inheritance
: Autosomal dominant
Cause
: Pathogenic germline mutations in the GLI3 gene.
Clinical sensitivity:
PHS - 90 percent; GCPS - 70 percent
Methodology
: Bidirectional sequencing of the entire coding region and intron/exon boundaries of the GLI3 gene.
Analytical sensitivity and specificity
: Greater than 99 percent for sequencing.
Limitations
: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations, deep intronic mutations, and large deletions/duplications are not detected. Exon 1 is a non-coding region and not covered by this assay. Mutations in genes other than GLI3 are not detected. 

Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.

Compliance Statement C: For human genetic inheritable conditions and mutations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Note
Hotline History
N/A
CPT Codes

81479

Components
Component Test Code* Component Chart Name LOINC
2011471 GLI3 Sequencing - Specimen 31208-2
2011472 GLI3 Sequencing - Interpretation 35474-6
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • Greig Cephalopolysyndactyly syndrome (GCPS)
  • Pallister-Hall syndrome (PHS)
  • polydactyly
GLI3-Related Disorders (GLI3) Sequencing