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Neurogenetics

19-03-2024 | Spastic Paraplegia | Original Article

Whole exome sequencing in Serbian patients with hereditary spastic paraplegia

Authors: Marija Brankovic, Vukan Ivanovic, Ivana Basta, Rin Khang, Eugene Lee, Zorica Stevic, Branislav Ralic, Radoje Tubic, GoHun Seo, Vladana Markovic, Ivo Bozovic, Marina Svetel, Ana Marjanovic, Nikola Veselinovic, Sarlota Mesaros, Milena Jankovic, Dusanka Savic-Pavicevic, Zita Jovin, Ivana Novakovic, Hane Lee, Stojan Peric

Published in: Neurogenetics

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Abstract  

Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases with a high genetic and clinical heterogeneity. Numerous HSP patients remain genetically undiagnosed despite screening for known genetic causes of HSP. Therefore, identification of novel variants and genes is needed. Our previous study analyzed 74 adult Serbian HSP patients from 65 families using panel of the 13 most common HSP genes in combination with a copy number variation analysis. Conclusive genetic findings were established in 23 patients from 19 families (29%). In the present study, nine patients from nine families previously negative on the HSP gene panel were selected for the whole exome sequencing (WES). Further, 44 newly diagnosed adult HSP patients from 44 families were sent to WES directly, since many studies showed WES may be used as the first step in HSP diagnosis. WES analysis of cohort 1 revealed a likely genetic cause in five (56%) of nine HSP families, including variants in the ETHE1, ZFYVE26, RNF170, CAPN1, and WASHC5 genes. In cohort 2, possible causative variants were found in seven (16%) of 44 patients (later updated to 27% when other diagnosis were excluded), comprising six different genes: SPAST, SPG11, WASCH5, KIF1A, KIF5A, and ABCD1. These results expand the genetic spectrum of HSP patients in Serbia and the region with implications for molecular genetic diagnosis and future causative therapies. Wide HSP panel can be the first step in diagnosis, alongside with the copy number variation (CNV) analysis, while WES should be performed after.
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Metadata
Title
Whole exome sequencing in Serbian patients with hereditary spastic paraplegia
Authors
Marija Brankovic
Vukan Ivanovic
Ivana Basta
Rin Khang
Eugene Lee
Zorica Stevic
Branislav Ralic
Radoje Tubic
GoHun Seo
Vladana Markovic
Ivo Bozovic
Marina Svetel
Ana Marjanovic
Nikola Veselinovic
Sarlota Mesaros
Milena Jankovic
Dusanka Savic-Pavicevic
Zita Jovin
Ivana Novakovic
Hane Lee
Stojan Peric
Publication date
19-03-2024
Publisher
Springer Berlin Heidelberg
Published in
Neurogenetics
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI
https://doi.org/10.1007/s10048-024-00755-x