Gene Symbol: FGFR3
Chromosomal Locus: 4p16
Protein: Fibroblast growth factor receptor 3
Pseudonyms: Nonsyndromic Craniodysmorphology
TURNAROUND TIME: 8 days
TESTING METHODOLOGY: Detection of a P250R (c.749C>G) mutation by PCR and restriction enzyme digestion.
- 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 refrigerated 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, but not required.
Incidence:1 in 30,000
Inheritance:75% of these cases are spontaneous; the remainder are inherited in an autosomal dominant manner.
Disease Characteristics: symptoms are extremely variable and can often mimic Crouzon, Pfeiffer or Saethre-Chotzen syndromes. However, unilateral craniosynostosis is common.
Molecular Genetic Mechanism: A single mutation, (P250R) in the Fibroblast Growth Factor Receptor 3 (FGFR3) gene is responsible for all cases of Muenke syndrome. The presence of the mutation is diagnostic.
Clinical Sensitivity: 100% (a diagnosis of Muenke syndrome is defined by the presence of a P250R mutation)
Analytic Sensitivity: 99%
INDICATIONS FOR USE:
- To determine whether Muenke Syndrome is responsible for the craniosynostosis in an affected individual.
- To establish whether the symptoms are spontaneous or inherited within a family.
- Prenatal testing is available to evaluate the risk of having an affected child.