Gene Symbol: FGFR3
Chromosomal Locus: 4p16
Protein: Fibroblast growth factor receptor 3
Pseudonyms: Nonsyndromic Craniosynostosis, Crouzondermoskeletal syndrome
TURNAROUND TIME: 10 days
TESTING METHODOLOGY: PCR amplification of exon 10 of the FGFR3 gene followed by DNA sequencing to detect variant p. A391E.
- 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 as a resource but not required.
Inheritance: Most patients have a denovo autosomal dominant mutation.
Disease Characteristics: Patients have classic features of Crouzon syndrome without the typical skeletal manifestations. The acanthosis nigricans is characterized by verrucous hyperplasia and hypertrophy of the skin with hyperpigmentation, especially in flexural areas. Both choanal atresia and hydrocephalus can also be present.
Molecular Genetic Mechanism: A single mutation, A391E in the Fibroblast Growth Factor Receptor, Type 3 (FGFR3) gene is responsible for all cases of Crouzon Syndrome with Acanthosis Nigricans in this gene. The presence of the mutation is diagnostic.
Clinical Sensitivity: 70% of this condition is associated with this specific locus. The remainder is found in very low incidence at many other loci.
Analytic Sensitivity: 99%
Test Limitations: Mutations outside the tested region of the gene will not be detected. Rare diagnostic errors can occur due to primer or probe site mutations or rare polymorphisms.
INDICATIONS FOR USE:
- To determine whether Crouzon Syndrome with Acanthosis Nigricans is responsible for a rash at flexure points on the body (knees, elbows neck).
- To determine whether Crouzon Syndrome with Acanthosis Nigricans is responsible for the craniosynostosis in an affected individual.
- Individuals at risk who wish prenatal diagnosis.