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

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

Aparna Ganapathy  1 , Avshesh Mishra  1 , Megha Rani Soni  1 , Priyanka Kumar  1 , Mukunth Sadagopan  1 , Anil Vittal Kanthi  1 , Irene Rosetta Pia Patric  1 , Sobha George  1 , Aparajit Sridharan  1 , T C Thyagarajan  1 , S L Aswathy  1 , H K Vidya  1 , Swathi M Chinnappa  1 , Swetha Nayanala  1 , Manasa B Prakash  1 , Vijayashree G Raghavendrachar  1 , Minothi Parulekar  1 , Vykuntaraju K Gowda  2 , Sheela Nampoothiri  3 , Ramshekhar N Menon  4 , Divya Pachat  5 , Vrajesh Udani  6 , Neeta Naik  7 , Mahesh Kamate  8 , A Radha Rama Devi  9 , P A Mohammed Kunju  10 , Mohandas Nair  11 , Anaita Udwadia Hegde  12 , M Pradeep Kumar  13 , Soumya Sundaram  4 , Preetha Tilak  14 , Ratna D Puri  15 , Krati Shah  16 , Jayesh Sheth  17 , Qurratulain Hasan  18 , Frenny Sheth  17 , Pooja Agrawal  1 , Shanmukh Katragadda  1 , Vamsi Veeramachaneni  1 , Vijay Chandru  1   19 , Ramesh Hariharan  1   19 , Ashraf U Mannan  20
Affiliations

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

Aparna Ganapathy et al. J Neurol. 2019 Aug.

Abstract

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.

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