Novel NOTCH3 mutation c.1564 T > A (p.Cys522Ser) presenting with early-onset Parkinsonism and white matter lesions
CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a hereditary small vessel disease caused by mutations in the NOTCH3 gene, characterized by recurrent strokes, cognitive decline, and psychiatric symptoms. This report presents a novel NOTCH3 c.156...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | Clinical Parkinsonism & Related Disorders |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590112525000015 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850122741678604288 |
|---|---|
| author | Nicola Rifino Silvia Baratta Esteban Zacarias Isabella Canavero Benedetta Storti Mario Stanziano Emanuela Maderna Gianluca Marucci Franco Taroni Anna Bersano |
| author_facet | Nicola Rifino Silvia Baratta Esteban Zacarias Isabella Canavero Benedetta Storti Mario Stanziano Emanuela Maderna Gianluca Marucci Franco Taroni Anna Bersano |
| author_sort | Nicola Rifino |
| collection | DOAJ |
| description | CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a hereditary small vessel disease caused by mutations in the NOTCH3 gene, characterized by recurrent strokes, cognitive decline, and psychiatric symptoms. This report presents a novel NOTCH3 c.1564 T > A (p.Cys522Ser) mutation associated with early-onset parkinsonism and significant white matter lesions. We describe a patient who presented with early-onset parkinsonism, characterized by bradykinesia and rigidity, alongside extensive white matter lesions observed through neuroimaging. Genetic testing revealed a novel c.1564 T > A (p.Cys522Ser) mutation in the NOTCH3 gene, contributing to the clinical diagnosis of CADASIL. This case underscores the phenotypic variability of CADASIL and the potential for atypical presentations, including parkinsonism. Early identification of genetic mutations can facilitate appropriate management and counseling for affected individuals and their families. Further research is warranted to explore the mechanisms underlying the association between NOTCH3 mutations and parkinsonism. Our findings contribute to the understanding of CADASIL, suggesting that clinicians should consider CADASIL in differential diagnoses of early-onset parkinsonism, especially in patients with concurrent white matter lesions. |
| format | Article |
| id | doaj-art-e9d008c721d8493ea90cd96a48da56cd |
| institution | OA Journals |
| issn | 2590-1125 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Clinical Parkinsonism & Related Disorders |
| spelling | doaj-art-e9d008c721d8493ea90cd96a48da56cd2025-08-20T02:34:46ZengElsevierClinical Parkinsonism & Related Disorders2590-11252025-01-011210029710.1016/j.prdoa.2025.100297Novel NOTCH3 mutation c.1564 T > A (p.Cys522Ser) presenting with early-onset Parkinsonism and white matter lesionsNicola Rifino0Silvia Baratta1Esteban Zacarias2Isabella Canavero3Benedetta Storti4Mario Stanziano5Emanuela Maderna6Gianluca Marucci7Franco Taroni8Anna Bersano9Cerebrovascular Unit Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy; Corresponding author at: Via Celoria 11, 20134 Milan, Italy.Unit of Medical Genetics and Neurogenetics Fondazione IRCCS Istituto Neurologico Carlo Besta Milan ItalyCerebrovascular Unit Fondazione IRCCS Istituto Neurologico Carlo Besta Milan ItalyCerebrovascular Unit Fondazione IRCCS Istituto Neurologico Carlo Besta Milan ItalyCerebrovascular Unit Fondazione IRCCS Istituto Neurologico Carlo Besta Milan ItalyNeuroradiology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta Milan ItalyNeuropathology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta Milan ItalyNeuropathology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta Milan ItalyUnit of Medical Genetics and Neurogenetics Fondazione IRCCS Istituto Neurologico Carlo Besta Milan ItalyCerebrovascular Unit Fondazione IRCCS Istituto Neurologico Carlo Besta Milan ItalyCADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a hereditary small vessel disease caused by mutations in the NOTCH3 gene, characterized by recurrent strokes, cognitive decline, and psychiatric symptoms. This report presents a novel NOTCH3 c.1564 T > A (p.Cys522Ser) mutation associated with early-onset parkinsonism and significant white matter lesions. We describe a patient who presented with early-onset parkinsonism, characterized by bradykinesia and rigidity, alongside extensive white matter lesions observed through neuroimaging. Genetic testing revealed a novel c.1564 T > A (p.Cys522Ser) mutation in the NOTCH3 gene, contributing to the clinical diagnosis of CADASIL. This case underscores the phenotypic variability of CADASIL and the potential for atypical presentations, including parkinsonism. Early identification of genetic mutations can facilitate appropriate management and counseling for affected individuals and their families. Further research is warranted to explore the mechanisms underlying the association between NOTCH3 mutations and parkinsonism. Our findings contribute to the understanding of CADASIL, suggesting that clinicians should consider CADASIL in differential diagnoses of early-onset parkinsonism, especially in patients with concurrent white matter lesions.http://www.sciencedirect.com/science/article/pii/S2590112525000015CADASILParkinsonismStrokeVariant of uncertain significance |
| spellingShingle | Nicola Rifino Silvia Baratta Esteban Zacarias Isabella Canavero Benedetta Storti Mario Stanziano Emanuela Maderna Gianluca Marucci Franco Taroni Anna Bersano Novel NOTCH3 mutation c.1564 T > A (p.Cys522Ser) presenting with early-onset Parkinsonism and white matter lesions Clinical Parkinsonism & Related Disorders CADASIL Parkinsonism Stroke Variant of uncertain significance |
| title | Novel NOTCH3 mutation c.1564 T > A (p.Cys522Ser) presenting with early-onset Parkinsonism and white matter lesions |
| title_full | Novel NOTCH3 mutation c.1564 T > A (p.Cys522Ser) presenting with early-onset Parkinsonism and white matter lesions |
| title_fullStr | Novel NOTCH3 mutation c.1564 T > A (p.Cys522Ser) presenting with early-onset Parkinsonism and white matter lesions |
| title_full_unstemmed | Novel NOTCH3 mutation c.1564 T > A (p.Cys522Ser) presenting with early-onset Parkinsonism and white matter lesions |
| title_short | Novel NOTCH3 mutation c.1564 T > A (p.Cys522Ser) presenting with early-onset Parkinsonism and white matter lesions |
| title_sort | novel notch3 mutation c 1564 t a p cys522ser presenting with early onset parkinsonism and white matter lesions |
| topic | CADASIL Parkinsonism Stroke Variant of uncertain significance |
| url | http://www.sciencedirect.com/science/article/pii/S2590112525000015 |
| work_keys_str_mv | AT nicolarifino novelnotch3mutationc1564tapcys522serpresentingwithearlyonsetparkinsonismandwhitematterlesions AT silviabaratta novelnotch3mutationc1564tapcys522serpresentingwithearlyonsetparkinsonismandwhitematterlesions AT estebanzacarias novelnotch3mutationc1564tapcys522serpresentingwithearlyonsetparkinsonismandwhitematterlesions AT isabellacanavero novelnotch3mutationc1564tapcys522serpresentingwithearlyonsetparkinsonismandwhitematterlesions AT benedettastorti novelnotch3mutationc1564tapcys522serpresentingwithearlyonsetparkinsonismandwhitematterlesions AT mariostanziano novelnotch3mutationc1564tapcys522serpresentingwithearlyonsetparkinsonismandwhitematterlesions AT emanuelamaderna novelnotch3mutationc1564tapcys522serpresentingwithearlyonsetparkinsonismandwhitematterlesions AT gianlucamarucci novelnotch3mutationc1564tapcys522serpresentingwithearlyonsetparkinsonismandwhitematterlesions AT francotaroni novelnotch3mutationc1564tapcys522serpresentingwithearlyonsetparkinsonismandwhitematterlesions AT annabersano novelnotch3mutationc1564tapcys522serpresentingwithearlyonsetparkinsonismandwhitematterlesions |