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Volume 09
Journal of Alzheimers Disease & Parkinsonism
ISSN: 2161-0460
Epilepsy 2019
Parkinsons Congress 2019
August 29-31, 2019
JOINT EVENT
conferenceseries
.com
August 29-31, 2019 Vienna, Austria
&
5
th
International Conference on
Epilepsy & Treatment
5
th
World Congress on
Parkinsons & Huntington Disease
Genetic landscape of malformations of cortical development with refractory epilepsy in Taiwan
Yo-Tsen Liu
National Yang-Ming University, Taiwan
M
alformations of cortical development (MCD) are a group of developmental disorders frequently causing
epilepsy. Although next generation sequencing can help identify substantial genetic variants, a correct genetic
diagnosis of MCD relies on the correlations with neuropathology. I will report the genetic landscape of MCD with
refractory epilepsy (RE) whose diagnosis were firmly established in a multidisciplinary epilepsy team at Taipei
Veterans General Hospital in Taiwan. Sixty-six patients were recruited. Their MCD types include: FCD (51, 77.3%),
heterotopia (4, 6.06%), polymicrogyri, Dandy-Walker malformation and lissencephaly. Tuberous sclerosis complex
was not included. These patients were first screened by targeted sequencing (TS) of 66 genes causative for MCD
and epilepsy encephalopathy. For those with a potential candidate variant identified, they were submitted to whole
exome sequencing to confirm the variant is the best pathogenic candidate. Reported pathogenic variant or novel
but potentially disease-causative variants were identified in 28 patients (42%). Among them, nine were familial
cases (32%). In the 38 genetic not-assigned individuals, only two had a positive family history (5.3%). Nine variants
(32/1%) occurred in the GATOR1 complex genes (DEPDC5/NPRL2/NPRL3). The hit rate was the highest, reaching
78% (7/9), in severe and diffuse MCD, like Dandy-Walker malformation and lissencephaly. For FCD, the hit rate
was 55% (28/51). Our results supported that rapid screening by tTS of known disease-causative genes is efficient to
enhance genetic diagnosis of MCD, particularly in severe and diffuse MCD and FCD. BrainMRI and neuropathology
are essential to determine the pathogenicity of identified variants.
Biography
Yo-Tsen Liu earned her MD at National Taiwan University, Taiwan and completed her neurological residency training and became a neurology consultant at Taipei
Veterans General Hospital (TVGH). After winning “Studying Abroad Scholarship” supported by Taiwan’s Ministry of Education, she studied her PhD at Institute of
Neurology, University College London, London, UK in 2010~2014. She is now a neurology consultant at Division of Epilepsy, Neurological Institute, TVGH and
Assistant professor at Faculty of Medicine and Institute of Brain Science, National Yang-Ming University, Taiwan. Her research interests are the applications of
next-generation sequencing in neurological diseases, focusing on epilepsy and movement disorders.
Yo-Tsen Liu, J Alzheimers Dis Parkinsonism 2019, Volume 09