Marfan Syndrome - FBN1 Gene

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MARFAN SYNDROME - FBN1 GENE

Gene Symbol: FBN1

Chromosomal Locus: 15q21.1
 
Protein: Fibrillin1
 
Related Syndromes: MASS syndrome, Shprintzen-Goldberg syndrome, Stiff skin syndrome, and Weill-Marchesani syndrome 2, dominant
 
Pseudonyms: fibrillin 1, fibrillin-15, MASS, WMS
 
TURNAROUND TIME: 4 weeks
  
TESTING METHODOLOGY: Polymerase chain reaction (PCR) followed by bidirectional sequencing of all 65 exon coding regions of the gene and the intron / exon borders.
 
SPECIMEN REQUIREMENTS:
  • 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.
A Molecular Genetics Laboratory Test Requisition must accompany the specimen. Contact the Molecular Laboratory at 918-502-1721 to obtain further information.
Note: Counseling and informed consent are recommended for genetic testing. A consent form is available as a resource but not required.
 
INTERPRETATIVE DATA:
 
Incidence: 1 in 5,000
 
Inheritance: Autosomal dominant. Approximately 75% of Marfan mutations are inherited from an affected parent, 25% are de-novo mutations.
 
Disease Characteristics: Marfan syndrome is a connective tissue disorder with striking pleiotropism and clinical variability. Cardiac features are dilatation of the aortic root, aneurysm of the aorta and aortic dissection. The cardiac symptoms often lead to premature death. Skeletal features are increased height, disproportionately long limbs, chest deformity, joint laxity, scoliosis and a narrow, highly arched palate with crowding of the teeth. Ocular features include myopia and ectopia lentis.
 
Molecular Genetic Mechanism: A variety of missense, nonsense and insertion/deletion mutations have been described throughout the gene.
 
 
Clinical Sensitivity: 70-90% of individuals with a clinical diagnosis of Marfan Syndrome can have a mutation in the coding regions of FBN1.
 
Analytical Sensitivity: 99%.
 
Test Limitations: Deletions of entire exons or the entire gene are not detected. Mutations that are not in the coding sequence of the FBN1 gene will not be detected. Rare diagnostic errors can occur due to primer or probe site mutations or rare polymorphisms.
 
INDICATIONS FOR USE:
  • To confirm a clinical diagnosis and clarify therapeutic options.
  • To evaluate the inheritance risk of aortic dissection and death in a family with known history.
  • To identify patients that are candidates for followup testing of TGFBR1 or TGFBR2.
  • Individuals at risk who wish prenatal diagnosis.
ADDITIONAL RESOURCES:
OMIM - Marfan syndrome: www.omim.org/entry/154700
OMIM - Shprintzen-Goldberg Craniosynostosis: www.omim.org/entry/182212
OMIM - Mass syndrome: www.omim.org/entry/604308
OMIM - Stiff skin syndrome: www.omim.org/entry/184900