Molecular Genetics Migraine and Strokes Panel

Strokes and migraines may have very similar sets of symptoms that include severe headache, vision loss, auras and weakness. This panel assesses the variants in genes associated with specific conditions where migraines and strokes are primary symptoms. These conditions include familial hemiplegic migraine, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) and others. These disorders can either be autosomal dominant or autosomal recessive.

Reasons for Referral:

• Confirm a clinical diagnosis with a genetic etiology for migraines and or strokes
• Carrier testing
• Positive family history

Next generation sequencing will analyze the exons or coding regions of 8 Migraine and Stroke-associated genes using Illumina NextSeq 500/550 technology.  Samples are prepared 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.

ATP1A2, CACNA1A, COL4A1, HTRA1, NOTCH3, POLG, SCN1A, SLC2A1 

• 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 a 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 CVS or Amniotic Fluid 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.

Weekly

6-8 weeks

• 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.

1. Genetics Home Reference: CADASIL https://ghr.nlm.nih.gov/condition/cerebral-autosomal-dominant-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy
2. Genetics Home Reference: CARASIL: https://ghr.nlm.nih.gov/condition/cerebral-autosomal-recessive-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy
3. Genetics Home Reference: Familial hemiplegic migraine https://ghr.nlm.nih.gov/condition/familial-hemiplegic-migraine