Most comprehensive test to confirm a clinical diagnosis of Pallister-Hall syndrome or Greig cephalopolysyndactyly syndrome.
- Patient Preparation
- Lavender (EDTA), pink (K2 EDTA), or Yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
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-75-85 percent
Methodology: Bidirectional sequencing of the entire coding region and intron/exon boundaries of the GLI3 gene. Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large exonic GLI3 deletions and duplications.
Analytical sensitivity and specificity: Greater than 99 percent for sequencing; greater than 98 percent for MLPA.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations, deep intronic mutations, and large deletions/duplications are not detected. The breakpoints of large deletions and duplications are not determined. 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.
|Component Test Code*||Component Chart Name||LOINC|
|2011466||GLI3 Seq/DelDup - Specimen||31208-2|
|2011467||GLI3 Seq/DelDup - Interpretation||35474-6|
- Greig Cephalopolysyndactyly syndrome (GCPS)
- Pallister-Hall syndrome (PHS)