Multi-gene testing in neurological disorders showed an improved diagnostic yield: data from over 1000 Indian patients

J Neurol. 2019 Aug;266(8):1919-1926. doi: 10.1007/s00415-019-09358-1. Epub 2019 May 8.


Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Genetic testing; Multi-gene panel; Neurological disorders; Next-generation sequencing.

MeSH terms

  • Child
  • Child, Preschool
  • Cohort Studies
  • Data Analysis*
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing / methods*
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • India / epidemiology
  • Male
  • Multifactorial Inheritance / genetics
  • Mutation / genetics
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / epidemiology
  • Nervous System Diseases / genetics*