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 will analyze the exons or coding regions of 42 Heterotaxia-associated genes using Illumina NextSeq 500 technology. Samples are prepared using hybridization probes to enrich exonic regions. Promoter, intronic, etc. regions are not assessed on our assay, but may contain variants that impact gene function.
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.
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)
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:
- Genetics Home Reference: Heterotaxy Syndrome https://ghr.nlm.nih.gov/condition/heterotaxy-syndrome#
Additional Info: