Connective Tissue Disorders Panel (14 Genes) Test Details
Inherited connective tissue disorders are a group of genetically heterogeneous diseases that primarily affect the skeletal and cardiovascular systems, though may also affect skin, joints, eyes, and other systems. Inheritance can be in an autosomal dominant, autosomal recessive, or X-linked manner. The Connective Tissue Disorders Panel sequences the coding regions and splice sites of 14 genes known to cause various connective tissue disorders with a large phenotypic overlap such as Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome type IV, and familial thoracic aortic aneurysm and dissection as well as the rarer conditions including Lujan-Fryns syndrome, Shprintzen-Goldberg syndrome, and Arterial tortuosity syndrome.
Available Connective Tissue Disorders Panel Tests
Connective Tissue Disorders Panel -14 genes
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|ACTA2||Actin, Alpha-2, Smooth Muscle, Aorta||102620||10q23.31|
|COL3A1||Collagen, Type III, Alpha-1||120180||2q32.2|
|MED12 (exon 22)||Mediator Complex Subunit 12||300188||Xq13.1|
|MYH11||Myosin, Heavy Chain 11, Smooth Muscle||160745||16p13.11|
|MYLK||Myosin Light Chain Kinase||600922||3q21.1|
|SKI||V-ski Avian Sarcoma Viral Oncogene Homolog||164780||1p36.33|
|SLC2A10||Solute Carrier Family 2 (Facilitated Glucose Transporter), Member 10||606145||20q13.12|
|SMAD3||Mothers Against Decapentaplegic, Drosophila, Homolog of, 3||603109||15q22.33|
|TGFβ2||Transforming Growth Factor, Beta-2||190220||1q41|
|TGFβR1||Transforming Growth Factor-Beta Receptor, Type I||190181||9q22.33|
|TGFβR2||Transforming Growth Factor-Beta Receptor, Type II||190182||3p24.1|
The Connective Tissue Disorders panel is best suited for individuals with syndromic features of a connective tissue disorder or those whose clinical diagnosis is not yet clear and may help shorten the “diagnostic odyssey.” The disease-specific sub-panel for TAAD should be ordered for individuals with isolated or Familial Thoracic Aortic Aneurysm and Aortic Dissection.
This test is performed by next generation sequencing using Agilent SureSelect capture followed by sequencing of the coding regions and splice sites using Illumina sequencing technologies. Variant calls are generated using the Burrows-Wheeler Aligner followed by Genomic Analysis Tool Kit (GATK) analysis. Detection of copy number variants (CNVs) encompassing 1 or more exons is performed using VisCap™ analysis. Sanger sequencing is used to fill in regions with insufficient coverage. All clinically significant variants are confirmed by Sanger sequencing or droplet digital PCR. Variants classified as likely benign or benign are not confirmed. This test does not detect variants in non-coding regions that could affect gene expression, aside from the splice junctions. CNV analysis is only performed when data meets necessary quality standards and may not be available for all cases.
If CNV analysis does not meet necessary quality standards, FBN1 deletion/duplication analysis is performed by multiplex ligation-dependent probe amplification (MLPA) to detect the presence or absence of a deletion or duplication of one or more exons spanning the FBN1 gene.
Analytical and Clinical Sensitivity
This test is 100.00% sensitive (525/525 variants tested; 95% CI = 99.27-100.00% ) to detect variants changing a single base and 100.00% sensitive to detect insertion/deletions 1-21 bp in size (17/17 variants tested; 95% CI = 81.57-100.00%). Regions with high sequence homology are included in this test if a unique Sanger sequencing assay can be designed to rule out false positive calls. Analytical sensitivity in these regions may be reduced.