Multi-gene testing in neurological disorders showed an improved diagnostic yield: data from over 1000 Indian patients
Neurological disorders are clinically heterogeneous group of disorders and are major causes of disability and death. Several of these disorders are caused due to genetic aberration. A precise and confirmatory diagnosis in the patients in a timely manner is essential for appropriate therapeutic and management strategies. Due to the complexity of the clinical presentations across various neurological disorders, arriving at an accurate diagnosis remains a challenge.
We sequenced 1012 unrelated patients from India with suspected neurological disorders, using TruSight One panel. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform.
We were able to detect mutations in 197 genes in 405 (40%) cases and 178 mutations were novel. The highest diagnostic rate was observed among patients with muscular dystrophy (64%) followed by leukodystrophy and ataxia (43%, each). In our cohort, 26% of the patients who received definitive diagnosis were primarily referred with complex neurological phenotypes with no suggestive diagnosis. In terms of mutations types, 62.8% were truncating and in addition, 13.4% were structural variants, which are also likely to cause loss of function.
In our study, we observed an improved performance of multi-gene panel testing, with an overall diagnostic yield of 40%. Furthermore, we show that NGS (next-generation sequencing)-based testing is comprehensive and can detect all types of variants including structural variants. It can be considered as a single-platform genetic test for neurological disorders that can provide a swift and definitive diagnosis in a cost-effective manner.
KeywordsNeurological disorders Genetic testing Next-generation sequencing Multi-gene panel
We thank the patients and families, who consented to participate in this study. We thank all the physicians, who referred the patients to our centre. We also thank the Strand Life Sciences laboratory, bioinformatics, interpretation and genetic counselling staff for providing the infrastructure needed for this study.
AG—acquisition of data, analysis of data, interpretation and critical review of data, drafting of manuscript. AV, MRS—acquisition of data, analysis of data, interpretation of data, making of figures. PK, MS, AVK, IRPP, SG, AS, TTC, ASL, VHK, SMC—acquisition of data, interpretation of data. VR, SN, RM, DP, VU, NN, MK, ARRD, MK, SJ, MN, AUH, MPP, SS, PT, RP, AH, KS, JS—acquisition of data and concept of the study. PA—acquisition of data, sequencing. SK, VV—analysis and validation. AM, AG—conception and design of study, analysis of data, interpretation and critical review of data, drafting of manuscript. AM, VC, RH—critical inputs and finalization of the manuscript. All authors contributed in preparation of the manuscript, read and approved the final manuscript.
For this study, funding was not obtained from any funding body; therefore, there is no role of any funding body in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
Compliance with ethical standards
Conflicts of interest
AG, AV, MRS, PK, MS, AVK, IRPP, SG, AS, TTC, ASL, VHK, SMC, SN, MBP, VGR, MP, PA, SK, VV, VC, RH, AM are employees of Strand Life Sciences that offer commercially available clinical genetic testing services.
Sequencing of patient samples used in the study has been approved by Institutional Ethics Committee of Strand Life Sciences.
Informed consent was obtained in writing from all subjects and sequencing of patient samples was approved by Institutional Ethics Committee of Strand Life Sciences.
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