Laboratory Test Information Guide

Details for CADASIL

Test Name: CADASIL
Alternate Name(s): Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy.
Laboratory: Molecular Diagnostics
Specimen Type: Whole blood-2 x 4 mL Lavender EDTA top Vacutainer tube
Collection Information: Blood samples must be maintained at room temperature.
Requisition: MOLECULAR DIAGNOSTIC REQUISITION
Test Schedule: As Required
Monday - Friday
0800 - 1600 h
Turnaround time from when specimen
is received in testing laboratory:
 
Routine
3 months
Stat
 
 
Reference Range: See report
Effective Date:  
Revised Date: 2019-04-29
Critical Value: N/A
Interpretive Comments: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)(PMID:9388399) is a cause of stroke and vascular dementia. It is a condition of mid-adulthood that can result from mutations in the Notch 3 gene on chromosome 19. These mutations can be identified by direct sequence analysis of the Notch3 coding sequence (PMID:16009764). The CADASIL screen offered in this laboratory involves analysis of the entire Notch3 coding region by direct sequence analysis of PCR-amplified leukocyte-derived genomic DNA, of exons 1 through 33 of this gene.

Special Processing:  
Comments: For more information click on:
MOLECULAR DIAGNOSTIC LABORATORY
Method of Analysis:  All coding exons and 20 bp of flanking intronic sequence are enriched using an LHSC custom targeted hybridization protocol (Roche Nimblegen), followed by high throughput sequencing (Illumina). Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software (SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; and Alamut Visual). All exons have >300x mean read depth coverage, with a minimum 100x coverage at a single nucleotide resolution. This assay meets the sensitivity and specificity of combined Sanger sequencing and MLPA copy number analysis. All variants interpreted as either ACMG category 1, 2, or 3 (pathogenic, likely pathogenic, VUS; PMID: 25741868) are confirmed using Sanger sequencing, MLPA, or other assays. ACMG category 4 and 5 variants (likely benign, benign) are not reported, but are available upon request. This assay has been validated at a level of sensitivity equivalent to the Sanger sequencing and standard copy number analysis (>99%; PMID: 27376475).
Critical Information Required: Pedigree required.
Storage & Shipment: Must be received in testing laboratory within 5 days of collection, shipped at room temperature by courier/overnight delivery.
System Codes: 
Cerner
 
 
Referred To:  

Questions? Comments? Contact Laura Gopaul