Akademik Veri Yönetim Sistemi
JOURNAL OF ISTANBUL FACULTY OF MEDICINE-ISTANBUL TIP FAKULTESI DERGISI, cilt.84, sa.4, ss.457-463, 2021 (ESCI)
Objective: 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>T; p.(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.