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Pediatrics - Cardiology

Houston, Texas

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Pediatrics - Cardiology
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FBN1 Mutation Analysis

Fibrillin-1 is an extracellular matrix glycoprotein that is the main component of the microfibrils. Fibrillin-1 is initially synthesized as profibrillin, which is cleaved near the carboxy-terminus to form the mature peptide. After maturation, fibrillin-1 forms homodimers. Fibrillin-1 is expressed in multiple connective tissues, where it provides force-bearing structural support, and it is encoded by the FBN1 gene, which is composed of 65 exons and is located at 15q21.1.

Fibrillin-1 Primary Structure

Multiple autosomal dominant mutations in FBN1 have been described for a wide spectrum of disease including complete and incomplete forms of Marfan syndrome, which is characterized by cardiovascular, skeletal and/or ocular manifestations with possible involvement of other systems (pulmonary, dura, integument and skin). FBN1 mutations have also been identified in patients with severe neonatal Marfan syndrome, isolated skeletal features of Marfan syndrome, autosomal dominant ectopia lentis and aortic aneurysm. With the exception of severe neonatal Marfan syndrome, which is typically caused by mutations in exons 24-32 of the FBN1 gene, strong genotype/phenotype correlations have not been identified. In addition, FBN1 mutations have been noted to demonstrate broad variable expressivity.

The John Welsh Cardiovascular Diagnostic Laboratory offers molecular genetic testing for FBN1 mutations. Individuals are tested by automatic fluorescent DNA sequencing of all 65 exons of the FBN1 gene. Genetic counseling is recommended for all individuals in order to identify additional at-risk family members and to discuss reproductive issues.

Reasons for Referral

Molecular confirmation of the diagnosis of Marfan syndrome, severe neonatal Marfan syndrome, isolated skeletal features of Marfan syndrome, autosomal dominant ectopia lentis, or aortic aneurysm.

Methodology

Genomic DNA is analyzed for FBN1 mutations by automatic fluorescent DNA sequencing of all 65 exons of the FBN1 gene, as well as the exon/intron junctions and a portion of the 5′ and 3′ untranslated regions. Patient DNA is sequenced in both the forward and reverse orientations. If a mutation is identified, additional family members are analyzed only for the familial mutation(s) by automatic fluorescent DNA sequencing.

Service Fees

Service Direct and Institutional Billing CPT Codes
Index Case (Full Gene) $1650 per sample 81408, G0452
Index Case - Neonatal MFS (Exons 24-33) $750 per sample 81405, G0452
Additional Family Members $300 per sample; known familial mutation only 81403, G0452

Sensitivity

DNA Sequencing Analysis: Approximately 98.4 percent detection of mutations in exons 1-65 of FBN1

Specimen Requirements

Blood (preferred): EDTA (purple-top) tubes: Adult: 5 cc, Child: 5 cc, Infant: 2-3 cc
Tissue: Frozen (preferred), RNAlater, Formalin-fixed, Paraffin-embedded
Other Body Fluids: Call to inquire
Buccal Swabs: One swab from each cheek

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