PhD Scientific Days 2022

Neurosciences I. (Poster discussion will take place in the Aula during the Coffee Break)

Genetic epidemiology analysis of NOTCH3 gene mutations in Hungary

Előadó neve

Szabó, Fruzsina, MSc

Előadó munkahelye

Institute of Genomic Medicine and Rare Disorders Semmelweis University

Előadó telefonszáma

06304147926

Előadó e-mail címe

fruzsi.szabo94@gmail.com

Az előadás címe

Genetic epidemiology analysis of NOTCH3 gene mutations in Hungary

Szerző(k) neve és munkahelye

Fruzsina Szabó, Institute of Genomic Medicine and Rare Disorders, Semmelweis Universitiy, Budapest,Hungary
Zoltan Grosz, Institute of Genomic Medicine and Rare Disorders, Semmelweis Universitiy, Budapest,Hungary
Peter Balicza, Institute of Genomic Medicine and Rare Disorders, Semmelweis Universitiy, Budapest,Hungary
Bence Gunda,Department of Neurology, Semmelweis Universitiy, Budapest, Hungary
Katalin Sas,Department of Neurology, Albert Szent-Györgyi Clinical Center, Faculty of Medicine, University of
Szeged
Vera Várhegyi,Institute of Genomic Medicine and Rare Disorders, Semmelweis Universitiy, Budapest,Hungary
Aniko Gal,Institute of Genomic Medicine and Rare Disorders, Semmelweis Universitiy, Budapest,Hungary
Molnar Maria Judit,Institute of Genomic Medicine and Rare Disorders, Semmelweis Universitiy, Budapest,Hungary

Bemutatás módja

Poszter

Szekció

Neurosciences I. (Poster discussion will take place in the Aula during the Coffee Break)

Language of the presentation

English

Preferred session

Neurosciences

Összefoglaló szövege

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary, small vessel disease causing stroke. The disease is frequently associated with migraine, progressive cognitive decline, and psychiatric disturbances. The worldwide prevalence of CADASIL has been estimated at approximately 2-4:100,000.
Aims:In this study, we investigated the frequency of pathogenic variants from the coding region of the NOTCH3 gene in Hungarian CADASIL patients and the associations of the pathogenic alterations with the detailed clinical phenotype and MRI findings.

Methods: Total coding region of the NOTCH3 gene was analysed with Sanger or NGS sequencing in 650 patients (359 male, 291 female; mean age 45.27±15.95 years) with small vessel disease features. Brain MRI showed multiple cerebral infarcts and white matter lesions in all cohorts and no risk factors for cerebrovascular abnormalities.

Results: In our study, in 52 of 650 patients (8%), 19 missense substitutions were identified. Among them, 4 were novel, likely pathogenic alterations (p. C222S, G420C, R133C, R207C), these variants were not present in controls and were predicted as disease causing by in silico analysis. The R90C mutation in exon 3 of NOTCH3 gene was the most frequently observed variant (68%), followed by R153C in exon 4 (21%). The clinical symptoms of the positive cases were divided into 4 groups. The most common symptom was TIA/stroke (69%), followed by migraine (52%) in approximately quarter of cases with aura, psychiatric disturbances (29%) and cognitive decline (25%). In retrospectively study of clinical data, we found a higher number of patients having leukoencephalopathy (86%) on brain MRI scans and the white matter lesions appear earlier on cranial MRI than symptoms of CADASIL.

Conclusion: The frequency of the variants was 8% In the Hungarian cohort the most common alteration was the R90C with 2.5% mutation frequency. These results broaden the genetic background and clinical spectrum of CADASIL in the Hungarian population. Based on our experiments, we recommend the genetic analysis of the NOTCH3 gene in patients with stroke / TIA, migraine and leukoencephalopathy.

Funding:The study was supported by the Semmelweis University StartUp, NKFIH_ 132812 and UNKP-21-5 grants.

University and Doctoral School

Semmelweis University, János Szentágothai Doctoral School of Neurosciences

Supervisor

Dr. Gál Anikó

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6935

Start

13:05

End

13:10

Authors (legacy)

Fruzsina Szabó, Institute of Genomic Medicine and Rare Disorders, Semmelweis Universitiy, Budapest,Hungary
Zoltan Grosz, Institute of Genomic Medicine and Rare Disorders, Semmelweis Universitiy, Budapest,Hungary
Peter Balicza, Institute of Genomic Medicine and Rare Disorders, Semmelweis Universitiy, Budapest,Hungary
Bence Gunda,Department of Neurology, Semmelweis Universitiy, Budapest, Hungary
Katalin Sas,Department of Neurology, Albert Szent-Györgyi Clinical Center, Faculty of Medicine, University of
Szeged
Vera Várhegyi,Institute of Genomic Medicine and Rare Disorders, Semmelweis Universitiy, Budapest,Hungary
Aniko Gal,Institute of Genomic Medicine and Rare Disorders, Semmelweis Universitiy, Budapest,Hungary
Molnar Maria Judit,Institute of Genomic Medicine and Rare Disorders, Semmelweis Universitiy, Budapest,Hungary