Salman, BarisYucesan, EmrahSamanci, BediaBilgic, BasarHanagasi, HasmetGurvit, IbrahimOzbek, UgurUgur Iseri, Sibel2023-02-212023-02-212021-01-0110.26650/IUITFD.2021.913346https://hdl.handle.net/11443/1894http://dx.doi.org/10.26650/IUITFD.2021.913346Objective: To explore the underlying genetic variations and mechanisms in a family affected by isolated dystonia. Material and Method: We employed whole genome Single Nu-cleotide Polymorphism (SNP) based linkage analysis along with whole exome sequencing (WES) in a consanguineous family pre -senting with isolated dystonia. An in-house pipeline compiled for WES analysis along with in-depth in silico prediction algo-rithms were used to assess the associated data produced in this study. Sanger sequencing was used for variant confirmation and segregation. Results: Data analysis included locus oriented WES variant prior-itization and cryptic splicing predictions. We detected a homo-zygous and synonymous variation rs748449895 (NM\_015125.4: c.4143C>Tp.(Thr1381=)) in the capicua transcriptional repres-sor, CIC. This variation disrupts the YB-1 RNA recognition motif and creates an alternative SRp20 RNA recognition motif. Conclusion: The resulting variant might cause the dystonia phe-notype by affecting the alternative splicing of CIC transcript and altering the exon inclusion motif which may disrupt the ATXN1- CIC complex.Autosomal recessive dystoniawhole genome genotypinglinkage analysiswhole exome sequencingalternative splicingArticleWOS:000704257000007