FBN1 Genetic Analysis, Known Mutation

CPT CODE:

  • "FBN1 Genetic Analysis, Known Mutation"
  • 83892/ Enzymatic digestion
  • 83894/ Separation by gel electrophoresis
  • 83898/ Amplification, target, each nucleic acid sequence
  • 83912/ Interpretation and report
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    USEFUL FOR:

    Genetic testing of individuals at risk for a known FBN1 mutation

    SPECIMEN REQUIRED:

    "FBN1 Gene Testing Patient Information Sheet" (SupplyT636) must be submitted with the specimen. See SpecialInstructions for a copy of the form.
    Draw blood in a lavender-top (EDTA) tube(s), and send 3 mL of EDTA whole blood in original VACUTAINER(S).Note:    1. Include physician name and phone number with                  the specimen.             2. Bone marrow transplants will interfere with testing.
                     For bone marrow transplant patients, buccal cells                  from the recipient should be provided to obtain an                  accurate genotype.             3.  Transfusions will interfere with testing for up to 4 to                 6 weeks. DNA obtained from white cells may not                 provide useful information for patients who received                 a recent transfusion of blood that was not leukocyte-                 reduced. Wait 4 to 6 weeks until transfused cells                 have left the patient's circulation before drawing the                  patient's blood specimen for genotype testing.4.  An "Informed Consent for DNA Testing" (Supply    T576) is available. See Special Instructions for a    copy of the form.

    TRANSPORT TEMPERATURE:

    Ambient\Frozen OK\Refrig OK

    CLINICAL INFORMATION:

    Fibrillin-1 is a 320-kD cysteine-rich glycoprotein found in theextracellular matrix. Monomers of fibrillin-1 associate to formmicrofibrils, which provide mechanical stability and elasticproperties to connective tissues. Fibrillin-1 is encoded by theFBN1 gene, which contains 65 exons and is located atchromosome 15q21.
    FBN1 mutations are most commonly associated with Marfansyndrome (MFS), an autosomal dominant connective tissuedisorder involving the ocular, skeletal, and cardiovascularsystems. Ocular MFS manifestations most commonly includemyopia and lens displacement. Skeletal manifestations caninclude arachnodactyly (abnormally long and slender fingersand toes), dolichostenomelia (long limbs), pectus (chest wall)deformity, and scoliosis. Cardiovascular manifestations, whichare the major cause of early morbidity and mortality in MFS,include aortic dilation and aortic aneurysm and dissection, aswell as mitral valve and tricuspid valve prolapse. There issignificant inter- and intra-familial variability in phenotype.
    FBN1 mutations have also been reported in several other rarephenotypes with variable overlap with classic MFS. Theseconditions include neonatal MFS, autosomal dominant ectopialentis (displacement of the lens of the eye), isolated ascendingaortic aneurysm and dissection, isolated skeletal features ofMFS, MASS phenotype (mitral valve prolapse, aortic diameterincreased, stretch marks, skeletal features of MFS),Shprintzen-Goldberg syndrome (Marfanoid-craniosynostosis[premature ossification and closure of sutures of the skull]), andautosomal dominant Weill-Marchesani syndrome (short statureand short fingers, ectopia lentis).
    Hundreds of mutations have been identified in FBN1, many ofthem unique to individual families. There is a wide range ofvariability, including intrafamilial variability, in expressivity amongFBN1 mutations. Approximately two thirds of FBN1 mutations aremissense mutations, with the majority of these being cysteinesubstitutions. Approximately 25% to 33% of FBN1 mutations arede novo mutations, in which an individual has no family history ofdisease. FBN1 mutations have been shown to occur across thegene with very few genotype-phenotype correlations, with theexception of the association of neonatal MFS and mutations inexons 24 through 32.
    Genetic testing for FBN1 mutations allows for the confirmationof a suspected genetic disease. Confirmation of MFS or otherFBN1-associated genetic diseases allows for proper treatmentan

    CLINICAL INTERPRETATION:

    An interpretive report will be provided.

    REFERENCE VALUES:

    An interpretive report will be provided.