Gene Symbol: FGFR3
Chromosomal Locus: 4p16.3
Protein: Fibroblast growth factor receptor 3 precursor
TURNAROUND TIME: 8 days
AMA 2012: 81401
TESTING METHODOLOGY: Detection of a G380R (c.1138G>A or G>C) 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 at 4°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: 1 in 15,000 to 40,000
Inheritance: More than 80% of ACH cases are due to a spontaneous mutation; the remainder are inherited in an autosomal dominant manner with 100% penetrance
Disease Characteristics: Achondroplasia is characterized by abnormal bone growth that results in short stature with disproportionately short arms and legs, a large head, and characteristic facial features. In infancy, hypotonia is typical, and development of motor milestones is often delayed. Intelligence and life span are usually normal.
Molecular Genetic Mechanism: More than 99% of individuals have a G380R substitution, which may result from a G>A/C point mutation at nucleotide 1138 of the FGFR3 gene.
Clinical Sensitivity: ~99%
Analytic Sensitivity: >99%
Test Limitations: Mutations that are not c.1138G>A or G>C will not be detected (less than 1%). Rare diagnostic errors can occur due to primer or probe site mutations or rare polymorphisms.
INDICATIONS FOR USE:
- To confirm the nature of dwarfism in an affected individual.
- To evaluate fetuses with abnormal ultrasound findings for the possibility of spontaneous Achondroplasia.
- Individuals at risk who wish prenatal diagnosis.