WAARDENBURG SYNDROME, TYPE 1 AND 3 - PAX 3 GENE
Gene Symbol: PAX3
Chromosomal Locus: 2q35
Protein: Paired Box 3
Pseudonyms: WS1, WS3
TURNAROUND TIME: 4 weeks
TESTING METHODOLOGY: Polymerase chain reaction (PCR) and DNA Sequencing of all 10 exons, and their intron- exon borders.
- Collect: Prefer two 5ml whole blood EDTA (lavender top) tube.
- Min. Collection: 0.7 ml whole blood EDTA.
- Transport: blood EDTA at Room Temp shipped regular next day air (No Saturday delivery; store specimen at 40°C and ship Monday).
- Stability: Ambient: up to 7 days; Refrigerated: 2 weeks. Frozen: unacceptable
- Unacceptable Conditions: Serum. Frozen or severely hemolyzed blood. Clotted blood.
- Prenatal testing: Direct: 5ml direct unspun amniotic fluid or 15mg CVS tissue with a backup flask growing. Culture: confluent T25 flask. Maternal blood sample is required for maternal cell contamination studies.
Counseling and informed consent are recommended for genetic testing. A consent form
is available as a resource but not required.
Incidence: Estimates range from 1:10,000 to 1:40,000
Inheritance: Autosomal dominant
Disease Characteristics: Congenital sensorineural hearing loss and pigmentary abnormalities of the iris, hair, and skin, along with dystopia canthorum. The hearing loss is typically non-progressive, sensorineural, and may be either unilateral or bilateral. An abnormality of hair pigmentation often seen is a white Forlocte. Symptoms are highly variable even within families.
Molecular Genetic Mechanism: A variety of missense, nonsense and insertion/deletion mutations have been described in the gene.
Clinical Sensitivity: 60-70% of WS.
Analytic Sensitivity: 99%
Test Limitations: Whole-gene or exonic deletions or duplications will not be detected (roughly 6%). Rare diagnostic errors can occur due to primer or probe site mutations or rare polymorphisms.
INDICATIONS FOR USE:
- To determine whether a hearing defect in a child is hereditary.
- To assess the risk of additional children with hearing loss in an affected family.
- Individuals at risk who wish prenatal diagnosis.