• Test Code:
    1610
  • Department:
    Molecular Genetics
  • Test Synonyms:
    Heterotaxy SyndromeACVR2BARMC4C21ORF59CCDC103CCDC114CCDC151CCDC39CCDC40CCDC65CCNOCENPFCITED2CRELD1DNAAF1DNAAF2DNAAF3DNAH11DNAH5DNAI1DNAI2DNAJB13DRC1DYX1C1FOXH1GAS8GATA4GDF1HEATR2LEFTY2LRRC6NKX2-5NODALPIH1D3RSPH1RSPH3RSPH4ARSPH9SHROOM3SMAD2SPAG1ZIC3ZMYND10
  • CPT Code(s):
    81479
Background:

Heterotaxy is a congenital condition diagnosed by abnormal arrangement of organs in the chest and abdomen. The arrangements of the organs are flipped where they are typically seen, a condition called situs inversus or situs amiguus. This mis-orientation may cause structural abnormalities of the organs.  The prevalence of these conditions is about 1:10,000 worldwide. These conditions may be sporadic or follow an autosomal dominant, recessive or X-linked pattern. This next-generation sequencing test assesses the coding regions of 42 genes associated with heterotaxy syndrome. 

Reasons for Referral:

  • Confirm a clinical diagnosis for a genetic etiology for heterotaxia
  • Carrier testing
  • Positive family history

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.

 

The 42 Heterotaxia-associated genes are listed below:
ACVR2B, ARMC4, C21ORF59, CCDC103, CCDC114,  CCDC151, CCDC39, CCDC40, CCDC65, CCNO, CENPF, CITED2, CRELD1, DNAAF1, DNAAF2, DNAAF3, DNAH11, DNAH5, DNAI1, DNAI2, DNAJB13, DRC1, DYX1C1, FOXH1, GAS8, GATA4, GDF1, HEATR2, LEFTY2, LRRC6, NKX2-5, NODAL, PIH1D3, RSPH1, RSPH3, RSPH4A, RSPH9, SHROOM3, SMAD2, SPAG1, ZIC3, ZMYND10

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 Kit(s) (OGR-500). Please contact KDL Client Services for a Saliva Collection Kit for patients that cannot provide a blood sample.

Assisted Saliva: 4 ORAgene™ Assisted Saliva Collection Kit(s) (OGR-575) used according to manufacturer instructions.  Please contact KDL Client Services for a 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.

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)
  • DNA: 10µg at a minimum of 60-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)


    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 (or saliva) in addition to the fetal specimen. Additional charges apply for the maternal cell rule-out test.
    For routine testing of blood and saliva (or DNA extracted from them), KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion.  For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.


    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:

    • Package and ship specimen to remain cold, but not frozen. 
    • Ship via overnight express, using the FedEx priority overnight label provided. 
    • Contact Client Services for shipping kits and instructions at (855) 535-1522.

    References:

    1. Genetics Home Reference: Heterotaxy Syndrome https://ghr.nlm.nih.gov/condition/heterotaxy-syndrome#

    Additional Info: