CADASIL: NOTCH3 gene analysis

Diagnostic Use

Defects in NOTCH3 are the cause of cerebral autosomal dominant arteriopathy with sub cortical infarcts and leukoencephalopathy (CADASIL) [MIM:125310]. CADASIL causes a type of stroke and dementia key features of which include recurrent sub-cortical ischemic events, migraine headaches (30–40% of individuals) and vascular dementia. The disorder affects relatively young adults of both sexes with most affected individuals having an affected parent. Mutations affect highly conserved cysteine residues within epidermal growth factor (EGF)-like repeat domains in the extracellular part of the receptor. The pathologic hallmark of CADASIL is electron-dense granules in the media of arterioles that can often be identified by electron microscopy of skin biopsies.

Department

Genetics - Molecular Pathology

Delphic Registration Code

MOLP

Constituent Tests

• Genomic DNA Extraction

Synonyms

NOTCH3

Turnaround Time

4 weeks

Test Code

4561

Specimen Type

• Whole Blood

Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

4.0

No of Samples Required

1

Paediatric Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

1.0

Minimum Sample Volume (ml)

0.5

Additional Specimen Information

This genetic analysis needs nucleated cells. Please don’t centrifuge or freeze the EDTA blood tube.
If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Aliquot Instructions

Sample Type

• Whole Blood

Transport to Lab

Ambient (8 - 24 degrees Celsius)

Additional Referral/Aliquot Information

This genetic analysis needs nucleated cells. Please don’t centrifuge or freeze the EDTA blood tube.
If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Interpretation

The finding of a previously described NOTCH3 sequence variant in a symptomatic individual supports a diagnosis of CADASIL. A negative result excludes >95% of CADASIL-causing sequence alterations in NOTCH3, which are missense variants characteristically leading to the loss or gain of a cysteine residue in one of the 34 EGFr domains (GeneReviews).

Reference Intervals

NCBI Reference sequence: NM_000435.2

Test Method

Patient DNA is analysed using an Ampliseq-for-Illumina next generation sequencing (NGS) custom panel on an Illumina MiSeq instrument, which targets the NOTCH3 gene implicated in CADASIL.

Non-Funded Test Cost

$728.43 (Exclusive of GST)

Billing Code

4561

Laboratories may prefer to submit DNA for testing. Please provide a minimum of 5 micrograms of DNA at 20 nanograms / microliter.

Contact Information

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