What factors determine phenotype of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)? Considerations in the context of a novel pathogenic R110C mutation in the NOTCH3 gene
We report patients from a Polish family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) who possess a novel heterozygous R110C mutation in exon 3 of the NOTCH3 gene leading to stereotypical cysteine loss. The proband had only seizure attacks...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Termedia Publishing House
2017-12-01
|
| Series: | Folia Neuropathologica |
| Subjects: | |
| Online Access: | https://www.termedia.pl/What-factors-determine-phenotype-of-cerebral-autosomal-dominant-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy-CADASIL-Considerations-in-the-context-of-a-novel-pathogenic-R110C-mutatio,20,31347,1,1.html |
| _version_ | 1818426669343440896 |
|---|---|
| author | Dorota Dziewulska Dorota Sulejczak Michalina Wężyk |
| author_facet | Dorota Dziewulska Dorota Sulejczak Michalina Wężyk |
| author_sort | Dorota Dziewulska |
| collection | DOAJ |
| description | We report patients from a Polish family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) who possess a novel heterozygous R110C mutation in exon 3 of the NOTCH3 gene leading to stereotypical cysteine loss. The proband had only seizure attacks and her magnetic resonance imaging (MRI) showed very numerous hyperintense foci in the cerebral white matter in a location characteristic of CADASIL. Distinctive ultrastructural assessment of vessels from skin-muscle biopsy revealed only mild degenerative changes but relatively numerous homogeneous deposits of granular osmiophilic material (GOM). In the other symptomatic family members with the same mutation ischaemic strokes were present but not epilepsy. In the proband’s affected brother at a similar age, the brain MRI was normal but vessels showed pronounced degenerative changes and irregular GOM deposits. The present report not only extends the list of known pathogenic mutations responsible for CADASIL but also emphasizes clinical and morphologic variability among family members with the same NOTCH3 mutation, suggesting that probably additional factors, not only mutations, may influence the disease phenotype. |
| first_indexed | 2024-12-14T14:33:30Z |
| format | Article |
| id | doaj.art-f4fe2bc10194426faa76844413e77c52 |
| institution | Directory Open Access Journal |
| issn | 1641-4640 1509-572X |
| language | English |
| last_indexed | 2024-12-14T14:33:30Z |
| publishDate | 2017-12-01 |
| publisher | Termedia Publishing House |
| record_format | Article |
| series | Folia Neuropathologica |
| spelling | doaj.art-f4fe2bc10194426faa76844413e77c522022-12-21T22:57:45ZengTermedia Publishing HouseFolia Neuropathologica1641-46401509-572X2017-12-0155429530010.5114/fn.2017.7238731347What factors determine phenotype of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)? Considerations in the context of a novel pathogenic R110C mutation in the NOTCH3 geneDorota DziewulskaDorota SulejczakMichalina WężykWe report patients from a Polish family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) who possess a novel heterozygous R110C mutation in exon 3 of the NOTCH3 gene leading to stereotypical cysteine loss. The proband had only seizure attacks and her magnetic resonance imaging (MRI) showed very numerous hyperintense foci in the cerebral white matter in a location characteristic of CADASIL. Distinctive ultrastructural assessment of vessels from skin-muscle biopsy revealed only mild degenerative changes but relatively numerous homogeneous deposits of granular osmiophilic material (GOM). In the other symptomatic family members with the same mutation ischaemic strokes were present but not epilepsy. In the proband’s affected brother at a similar age, the brain MRI was normal but vessels showed pronounced degenerative changes and irregular GOM deposits. The present report not only extends the list of known pathogenic mutations responsible for CADASIL but also emphasizes clinical and morphologic variability among family members with the same NOTCH3 mutation, suggesting that probably additional factors, not only mutations, may influence the disease phenotype.https://www.termedia.pl/What-factors-determine-phenotype-of-cerebral-autosomal-dominant-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy-CADASIL-Considerations-in-the-context-of-a-novel-pathogenic-R110C-mutatio,20,31347,1,1.html<i>CADASIL GOM microangiopathy NOTCH3 seizures</i> |
| spellingShingle | Dorota Dziewulska Dorota Sulejczak Michalina Wężyk What factors determine phenotype of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)? Considerations in the context of a novel pathogenic R110C mutation in the NOTCH3 gene Folia Neuropathologica <i>CADASIL GOM microangiopathy NOTCH3 seizures</i> |
| title | What factors determine phenotype of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)? Considerations in the context of a novel pathogenic R110C mutation in the NOTCH3 gene |
| title_full | What factors determine phenotype of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)? Considerations in the context of a novel pathogenic R110C mutation in the NOTCH3 gene |
| title_fullStr | What factors determine phenotype of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)? Considerations in the context of a novel pathogenic R110C mutation in the NOTCH3 gene |
| title_full_unstemmed | What factors determine phenotype of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)? Considerations in the context of a novel pathogenic R110C mutation in the NOTCH3 gene |
| title_short | What factors determine phenotype of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)? Considerations in the context of a novel pathogenic R110C mutation in the NOTCH3 gene |
| title_sort | what factors determine phenotype of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy cadasil considerations in the context of a novel pathogenic r110c mutation in the notch3 gene |
| topic | <i>CADASIL GOM microangiopathy NOTCH3 seizures</i> |
| url | https://www.termedia.pl/What-factors-determine-phenotype-of-cerebral-autosomal-dominant-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy-CADASIL-Considerations-in-the-context-of-a-novel-pathogenic-R110C-mutatio,20,31347,1,1.html |
| work_keys_str_mv | AT dorotadziewulska whatfactorsdeterminephenotypeofcerebralautosomaldominantarteriopathywithsubcorticalinfarctsandleukoencephalopathycadasilconsiderationsinthecontextofanovelpathogenicr110cmutationinthenotch3gene AT dorotasulejczak whatfactorsdeterminephenotypeofcerebralautosomaldominantarteriopathywithsubcorticalinfarctsandleukoencephalopathycadasilconsiderationsinthecontextofanovelpathogenicr110cmutationinthenotch3gene AT michalinawezyk whatfactorsdeterminephenotypeofcerebralautosomaldominantarteriopathywithsubcorticalinfarctsandleukoencephalopathycadasilconsiderationsinthecontextofanovelpathogenicr110cmutationinthenotch3gene |