Clinical presentation of Y189C mutation of the NOTCH3 gene in the Polish family with CADASIL

Jolanta Dorszewska; Marta Kowalska; Tomasz Grzegorski; Dorota Dziewulska; Katarzyna Karmelita-Katulska; Anna-Maria Barciszewska; Michał Prendecki; Wojciech Gorczyński; Wojciech Kozubski

doi:10.5114/fn.2020.94009

eISSN: 1509-572x
ISSN: 1641-4640

Folia Neuropathologica

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1/2020
vol. 58

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abstract:

Case report

Clinical presentation of Y189C mutation of the NOTCH3 gene in the Polish family with CADASIL

Jolanta Dorszewska

¹

,

Marta Kowalska

¹

,

Tomasz Grzegorski

^{2, 3}

,

Dorota Dziewulska

^{4, 5}

,

Katarzyna Karmelita-Katulska

⁶

,

Anna-Maria Barciszewska

⁷

,

Michał Prendecki

¹

,

Wojciech Gorczyński

²

,

Wojciech Kozubski

²

Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland
Chair and Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland
Department of Clinical Neuroimmunology, Poznan University of Medical Sciences, Poznan, Poland
Department of Experimental and Clinical Neuropathology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
Department of Neurology, Medical University of Warsaw, Poland
Department of General Radiology and Neuroradiology, Poznan University of Medical Sciences, Poznan, Poland
Department and Clinic of Neurosurgery and Neurotraumatology, Poznan University of Medical Sciences, Poznan, Poland

Folia Neuropathol 2020; 58 (1): 83-92

DOI: https://doi.org/10.5114/fn.2020.94009

Online publish date: 2020/03/31

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Introduction
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary, progressive ischemic disease of small vessels of the brain characterized by migraine with aura (MA), recurrent subcortical ischemic episodes, cognitive decline and psychiatric disorders. CADASIL is caused by mutations in the NOTCH3 gene. We identified the NOTCH3 Y189C mutation as a genetic cause of CADASIL in a Polish family and provided its first clinical manifestation.

Material and methods
The study included twelve subjects from one family. The NOTCH3 mutation, APOE and MTHFR polymorphisms were determined by high-resolution melting analyses (HRMA) and Sanger sequencing. Neuroimaging included CT and MRI. Ultrastructural examination of skin-muscle biopsy material of the proband was performed.

Results
The NOTCH3 Y189C mutation was present in a 36-year-old woman and her two sisters (aged 40 and 27) from 6 siblings. The MA was found in all of them, and started or became more severe after childbirth. The numerous T2/FLAIR hyperintense lesions were shown in the brain MRI. The deposition of granular osmiophilic material in the wall of small vessels of the proband observed in histopathological analysis confirmed the high degree of CADASIL severity.

Conclusions
Patients with the Y189C mutation of NOTCH3 from the same family display a similar phenotype of CADASIL.

keywords:

Clinical presentation of Y189C mutation of the NOTCH3 gene in the Polish family with CADASIL

Jolanta Dorszewska 1 , Marta Kowalska 1 , Tomasz Grzegorski 2, 3 , Dorota Dziewulska 4, 5 , Katarzyna Karmelita-Katulska 6 , Anna-Maria Barciszewska 7 , Michał Prendecki 1 , Wojciech Gorczyński 2 , Wojciech Kozubski 2

NOTCH3, Y189C mutation, CADASIL, clinical pattern

Jolanta Dorszewska

¹

,

Marta Kowalska

¹

,

Tomasz Grzegorski

^{2, 3}

,

Dorota Dziewulska

^{4, 5}

,

Katarzyna Karmelita-Katulska

⁶

,

Anna-Maria Barciszewska

⁷

,

Michał Prendecki

¹

,

Wojciech Gorczyński

²

,

Wojciech Kozubski

²