CADASIL analysis in cooperation with the Institute for Stroke and Dementia Research
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We are pleased to announce the cooperation with the Institute for Stroke and Dementia Research (ISD) for CADASIL analysis.
The ISD is designed as a novel type of research institute bridging the traditional barriers between academic medicine and basic science. By bringing together a critical mass of excellent scientist and clinicians the ISD facilitates the transfer of basic research findings into clinical applications (bench to bedside) while focussing basic research on clinically relevant questions (bedside to bench).
Centogene is offering for clinical and scientific partners of the ISD a high-end technological genetic service based on its international and national accreditation lines (CAP, CLIA, ISO).
The rapid technological developments in molecular genetic analysis has driven the cooperation between Centogene, together with its partner laboratory, Humangenetik Freiburg, and ISD.
To download the request form for CADASIL testing (german only), please click here.
Centogene ensures with its unique medical interpretation, its international accreditations and its state-of-the-art-technologies the highest level of genetic diagnostics, including full gene sequencing of the Notch3-gene as well as offering hot spot analysis and deletion/duplication testing.
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common inherited cause of stroke and vascular dementia in adults. Clinical and neuroimaging features resemble those of sporadic small-artery disease, although patients with CADASIL have an earlier age at onset of stroke events, an increased frequency of migraine with aura, and a slightly variable pattern of ischaemic white matter lesions on brain MRI. Notch3 (Notch homolog 3), the gene involved in CADASIL, encodes a transmembrane receptor primarily expressed in systemic arterial smooth-muscle cells. Pathogenetic mutations alter the number of cysteine residues in the extracellular domain of Notch3, which accumulates in small arteries of affected individuals. Functional and imaging studies in cultured cells, genetically engineered mice, and patients with CADASIL have all provided insights into the molecular and vascular mechanisms underlying this disease.
The clinical presentation of CADASIL varies among and within families. The disease is characterized by five main symptoms: migraine with aura, subcortical ischemic events, mood disturbances, apathy, and cognitive impairment.
Migraine with aura occurs in 20%-40% of individuals with CADASIL. When present, it is the first symptom with a mean age of onset of 30 years (age range 6-48 years). In 50% of cases, atypical attacks occur with prolonged, basilar or hemiplegic aura and confusion, fever, meningitis or coma.
Transient ischemic attacks and ischemic stroke occur at a mean age of 47 years (age range 20-70 years), in most cases without conventional vascular risk factors. Ischemic event are subcortical and present in most individuals as lacunar syndromes.
Imaging abnormalities in CADASIL evolve as the disease progresses and MRI findings report white matter hyperintensities, symmetrically distributed and located in the periventricular and deep white matter. The pattern of lesions is similar to age-related small vessel disease with only one exception: The occurrence of lesions at the temporal pole is a characteristic sign of CADASIL.
Notch3 is the only gene in which mutations are known to cause CADASIL. Most mutations in Notch3 in individuals with CADASIL are located in exon 4, followed by exons 3, 5, 6, and 11.
To find out more about CADASIL and the Notch3-gene, please refer to the following publications:
- Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser M-G. CADASIL. Lancet Neurol; 2009 Jul 1;8(7):643–53.
- Opherk C, Peters N, Herzog J, Luedtke R, Dichgans M. Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients. Brain. 2004 Nov;127(Pt 11):2533–9.
- Joutel A, Monet-Leprêtre M, Gosele C, Baron-Menguy C, Hammes A, Schmidt S, et al. Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease. J Clin Invest. 2010 Feb 1;120(2):433–45.
- Duering M, Karpinska A, Rosner S, Hopfner F, Zechmeister M, Peters N, et al. Co-aggregate formation of CADASIL-mutant NOTCH3: a single-particle analysis. Hum Mol Genet. 2011 Jul 21;20(16):3256–65.