Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, CADASIL (NOTCH3), Sequencing

Casandra

Casandra Test Code AR37994Version 1 (DRAFT)

Performing Lab

Lab ARUP LaboratoriesLab Test ID 3004383CPT Code 81406

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, CADASIL (NOTCH3), Sequencing

Also known as: NOTCH3 NGS

Clinical Use

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Use

The test is designed for the genetic confirmation of a clinical diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). CADASIL is characterized by subcortical ischemic events, such as transient ischemic attacks (TIAs) and strokes, with other features including cognitive defects, dementia, migraines, psychiatric disorders, and epilepsy. The condition exhibits high variability in age of onset and clinical presentation. Pathogenic variants in the NOTCH3 gene are the known cause, and the prevalence is estimated at 2-4 in 100,000 with autosomal dominant inheritance. The clinical sensitivity of this test is 95%, detecting single nucleotide variants with high accuracy.

Special Instructions

Testing minors for adult-onset conditions is not recommended, and it requires prior approval. Patients from New York State must submit specimens to a New York-approved laboratory. An Informed Consent for Genetic Testing and a CADASIL Testing Patient History Form are required. Genetic consultation is recommended for interpreting results, especially in the context of family history.

Limitations

This test detects variants only in the coding regions and exon-intron boundaries of the NOTCH3 gene. Regulatory region and deep intronic variants are not identified. The test does not detect all deletions, duplications, or insertions and may have reduced sensitivity in pseudogenes or repetitive regions. It may not identify low-level mosaic or somatic variants and is not suitable for patients with recent allogeneic stem cell transplantation. The test does not sequence NOTCH3 exon 1 due to technical limitations.

Test Details