Whole exome and targeted gene sequencing to detect pathogenic recessive variants in early onset cerebellar ataxia.
Over 100 genetically distinct causal known loci for hereditary ataxia phenotype poses a challenge for diagnostic work-up for ataxia patients in a clinically relevant time and precision. In the present study using next-generation sequencing, we have investigated pathogenic variants in early-onset cerebellar ataxia cases using whole exome sequencing in singleton/family-designed and targeted gene-panel sequencing. A total of 98 index patients were clinically and genetically (whole exome sequencing (WES) in 16 patients and targeted gene panel of 41 ataxia causing genes in 82 patients) evaluated. Four families underwent WES in family based design. Overall, we have identified 24 variants comprising 20 pathogenic and four likely-pathogenic both rare/novel, variations in 21 early onset cerebellar ataxia patients. Among the identified variations, SACS (n = 7) and SETX (n = 6) were frequent, while ATM (n = 2), TTPA (n = 2) and other rare loci were observed. We have prioritized novel pathogenic variants in RARS2 and FA2H loci through family based design in two out of four families.
['Shakya|Sunil|S|', 'Kumari|Renu|R|', 'Suroliya|Varun|V|', 'Tyagi|Nishu|N|', 'Joshi|Aditi|A|', 'Garg|Ajay|A|', 'Singh|Inder|I|', 'Kalikavil Puthanveedu|Divya|D|', 'Cherian|Ajith|A|', 'Mukerji|Mitali|M|', 'Srivastava|Achal K|AK|', 'Faruq|Mohammed|M|0000-0001-8278-8396']
D000328:Adult D001483:Base Sequence D005190:Family D005808:Genes, Recessive D056426:Genetic Loci D020022:Genetic Predisposition to Disease D014644:Genetic Variation D006801:Humans D009154:Mutation D013132:Spinocerebellar Degenerations D000073359:Whole Exome Sequencing
whole exome sequencing India ataxia genetics autosomal recessive cerebellar ataxia targeted sequencing