Molecular Genetics Connective Tissue Panel

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Test Code:

1165
Department:

Molecular Genetics
Test Synonyms:

Marfan Syndrome • Loeys-Dietz Syndrome (LDS) • Ehlers-Danlos Syndrome • Familial Aneurysm and Aortopathy • Shprintzen-Goldberg Syndrome • ACTA2 • ADAMTS2 • B3GALT6 • B4GALT7 • CBS • CHST14 • COL1A1 • COL1A2 • COL3A1 • COL5A1 • COL5A2 • FBN1 • FBN2 • FKBP14 • FLNA • MED12 • MYH11 • MYLK • NOTCH1 • PLOD1 • PRDM5 • SKI • SLC2A10 • SLC39A13 • SMAD3 • TGFB2 • TGFB3 • TGFBR1 • TGFBR2 • TNXB • ZNF469
CPT Code(s):

81408

Background:

The inherited connective tissue disorders comprise a group of genetically heterogeneous diseases including: Marfan syndrome, Loeys-Dietz syndrome, and Ehlers-Danlos syndrome. This group of disorders primarily affects the skeletal and cardiovascular systems. Marfan syndrome is a clinically variable disorder involving the cardiovascular, ocular, and skeletal systems. Primary manifestations for Marfan syndrome include aortic dilation and/or dissection, myopia, retinal detachment, glaucoma, bone overgrowth, and joint laxity. Loeys-Dietz syndrome is characterized by skeletal abnormalities with aneurysms and/or dissections of the cerebral, thoracic, and abdominal arteries. Ehlers-Danlos syndrome is a disorder defined by smooth, hyperelastic skin, abnormal wound healing and bruising, joint hypermobility, and risk for arterial rupture. This next-generation sequencing test is designed to detect mutations in the coding region of 31 genes associated with Connective Tissue Disorders.

Reasons for Referral:

Aortic or arterial aneurysms and/or dissections.
Clinical presentation consistent with Marfan syndrome, Loeys-Dietz Syndrome, or Ehlers-Danlos Syndrome.
Positive family history for connective tissue disorders (targeted testing is available if familial mutation is known).
Carrier testing.

Methodology:

Next generation sequencing (NGS) will analyze the exons or coding regions of the genes using Illumina NextSeq 500/550 technology and preparing samples using hybridization probes to enrich exonic regions. This assay does not assess regions of insufficient coverage, introns and promoter regions; pseudogenes; where the reference genome is inaccurate or contains gaps and insertions; and regions of high GC or polynucleotide repeats, but may contain variants that impact gene function.

Exon-level deletion/duplication analysis is performed by running the NGS data through the Genome Analysis Toolkit (GATK) Germline Copy Number Variation best practices pipeline from GATK, version 4.1.4.1. A Bayesian model was validated clinically in our lab. The model can detect copy changes at a resolution of three (3) or more probe targets (exons) for deletions and duplications in genes that do not have pseudogenes, and is not designed to detect low-level mosaicism or balanced alterations.

Connective Tissue Panel (31 genes): ACTA2, ADAMTS2, B3GALT6, B4GALT7, CBS, CHST14, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, FBN1, FBN2, FKBP14, FLNA, MED12, MYH11, MYLK, NOTCH1, PLOD1, PRDM5, SKI, SLC2A10, SLC39A13, SMAD3, TGFB2, TGFB3, TGFBR1, TGFBR2, TNXB, ZNF469

Specimen Requirements:

Blood: EDTA or ACD (Solution A or B):

Adult: 5 mL
Child: 5 mL
Infant: 2-3 mL

Saliva: 2 ORAgene™ Saliva Collection Kits (OGR-500) used according to manufacturer instructions. Please contact KDL Client Services for an Assisted Saliva Collection Kit for patients that cannot provide a blood sample.

Assisted Saliva: 4 ORAgene™ Assisted Saliva Collection Kits (OGR-575) used according to manufacturer instructions. Please contact KDL Client Services for an Assisted Saliva Collection Kit for patients that cannot provide a blood sample.

Skin Fibroblast: Punch Biopsy (Cell cultures will be prepared at KDL and used for testing), or 2 T-25 confluent flasks

DNA: 3-4µg at a minimum of 50-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

Prenatal
- Direct Amniotic Fluid (10-20mL)
- Direct CVS
- Direct POC
- Cultured Amniocytes (2 T-25 flasks
- Cultured CVS (2 T-25 flasks)
- Cultured Fetal Tissue: Product of Conception (2 T-25 flasks)
- Cord Blood (1-2mL)
Notice Regarding Molecular Genetic Testing on Prenatal Specimens:
Maternal cell rule-out testing will be performed on all prenatal specimens received. Please provide maternal blood in addition to the fetal specimen. Additional charges apply for the maternal cell rule-out test.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES. Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):

Weekly

Turn Around Time:

8 weeks

Shipment Sensitivity Requirements: