| Autor: |
Mandler, Julia M., Härtl, Johanna, Cordts, Isabell, Sturm, Marc, Hedderich, Dennis M., Bafligil, Cemsel, Baki, Enayatullah, Becker, Benedikt, Machetanz, Gerrit, Haack, Tobias B., Berthele, Achim, Hemmer, Bernhard, Deschauer, Marcus |
| Předmět: |
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| Zdroj: |
Multiple Sclerosis Journal - Experimental, Translational & Clinical; 7/24/2024, p1-12, 12p |
| Abstrakt: |
Background: Multiple sclerosis (MS) shares clinical/radiological features with several monogenic diseases that can mimic MS. Objective: We aimed to determine if exome sequencing can identify monogenic diseases in patients diagnosed with MS according to the McDonald criteria thus uncovering them as being misdiagnosed. Methods: We performed whole exome sequencing in a cohort of 278 patients with MS, clinically or radiologically isolated syndrome without cerebrospinal fluid-specific oligoclonal bands (CSF-OCBs) (n = 228), a positive family history of MS (n = 44), or both (n = 6), thereby focusing on individuals potentially more likely to have underlying monogenic conditions mimicking MS. We prioritized 495 genes associated with monogenic diseases sharing features with MS. Results: A disease-causing variant in NOTCH3 was identified in one patient without CSF-OCBs, no spinal lesions, with non-response to immunotherapy, and a family history of dementia, thereby converting the diagnosis to cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Moreover, 18 patients (6.5% of total) carried variants of unclear significance. Conclusion: Monogenic diseases being misdiagnosed as MS seem rare in patients diagnosed with MS according to the McDonald criteria, even in CSF-OCB negative cases. The detected pathogenic NOTCH3 variant emphasizes CADASIL as a rare differential diagnosis and highlights the relevance of genetic testing in selected MS cases with atypical presentations. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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