Four Novel Disease-Causing Variants in the NOTCH3 Gene in Russian Patients with CADASIL.
| Title: | Four Novel Disease-Causing Variants in the NOTCH3 Gene in Russian Patients with CADASIL. |
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| Authors: | Bostanova F; Research Centre for Medical Genetics, Moscow 115522, Russia.; Tsygankova P; Research Centre for Medical Genetics, Moscow 115522, Russia.; Nagornov I; Research Centre for Medical Genetics, Moscow 115522, Russia.; Dadali E; Research Centre for Medical Genetics, Moscow 115522, Russia.; Bessonova L; Research Centre for Medical Genetics, Moscow 115522, Russia.; Kulesh A; Department of Neurology and Medical Genetics, Vagner Perm State Medical University, Perm 614990, Russia.; Drobakha V; Department of Neurology and Medical Genetics, Vagner Perm State Medical University, Perm 614990, Russia.; Danchenko I; Perm Regional Clinical Hospital Perm Multiple Sclerosis Center, Perm 614015, Russia.; Kanivets I; Medical Center Genomed, Perm 614036, Russia.; Zakharova E; Research Centre for Medical Genetics, Moscow 115522, Russia. |
| Source: | Genes [Genes (Basel)] 2023 Aug 28; Vol. 14 (9). Date of Electronic Publication: 2023 Aug 28. |
| Publication Type: | Case Reports; Journal Article |
| Language: | English |
| Journal Info: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101551097 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4425 (Electronic) Linking ISSN: 20734425 NLM ISO Abbreviation: Genes (Basel) Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel : MDPI |
| MeSH Terms: | Receptor, Notch3*/genetics ; CADASIL*/genetics ; CADASIL*/pathology; Humans ; Male ; Female ; Middle Aged ; Adult ; Mutation, Missense ; Pedigree ; Russia ; Exons ; Mutation |
| Abstract: | Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease with unknown mechanisms and a broad phenotypic spectrum. It is caused by pathogenic variants in the NOTCH3 gene. The symptoms of the disease mainly include recurrent strokes with vascular risk factors, migraine with aura, dementia, and mood disturbances.; Case Presentation: Peripheral blood samples were collected from five patients from four unrelated families to extract genomic DNA. In four patients, analysis of exons 2, 3, 4, 5, 6 and adjacent intronic regions of the NOTCH3 gene was made via Sanger sequencing. Two previously undescribed nucleotide variants were identified in two patients: missense variant c.208G>T, (p.Gly70Cys) in exon 1 and splice-site variant c.341-1G>C in intron 3. Further DNA of two other patients were analyzed using a next-generation sequencing-based custom AmpliSeq™ panel for 59 genes associated with leukodystrophies. Two novel missense variants in the NOTCH3 gene were identified, c.1136G>A, (p.Cys379Tyr) in exon 7 and c.1547G>A, (p.Cys516Tyr) in exon 10. The pathogenic variant c.1547G>A, (p.Cys516Tyr) was confirmed in the fifth patient (family case) by Sanger sequencing. All patients had a history of headaches, transient ischemic attacks, memory impairment, and characteristics of MRI results. Three patients had strokes and two patients had psychiatric symptoms.; Conclusion: We found four previously undescribed pathogenic variants in the NOTCH3 gene in five patients with CADASIL and described their clinical and genetic characteristics. These results expand the mutational spectrum of CADASIL. |
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| Contributed Indexing: | Keywords: CADASIL; next-generation sequencing (NGS); targeted gene sequencing; the NOTCH3 gene |
| Substance Nomenclature: | 0 (Receptor, Notch3); 0 (NOTCH3 protein, human) |
| Entry Date(s): | Date Created: 20230928 Date Completed: 20260310 Latest Revision: 20260312 |
| Update Code: | 20260312 |
| PubMed Central ID: | PMC10531103 |
| DOI: | 10.3390/genes14091715 |
| PMID: | 37761855 |
| Database: | MEDLINE |
Case Reports; Journal Article