학술논문
Multi-gene testing in neurological disorders showed an improved diagnostic yield: data from over 1000 Indian patients
Document Type
Original Paper
Author
Ganapathy, Aparna; Mishra, Avshesh; Soni, Megha Rani; Kumar, Priyanka; Sadagopan, Mukunth; Kanthi, Anil Vittal; Patric, Irene Rosetta Pia; George, Sobha; Sridharan, Aparajit; Thyagarajan, T. C.; Aswathy, S. L.; Vidya, H. K.; Chinnappa, Swathi M.; Nayanala, Swetha; Prakash, Manasa B.; Raghavendrachar, Vijayashree G.; Parulekar, Minothi; Gowda, Vykuntaraju K.; Nampoothiri, Sheela; Menon, Ramshekhar N.; Pachat, Divya; Udani, Vrajesh; Naik, Neeta; Kamate, Mahesh; Devi, A. Radha Rama; Mohammed Kunju, P. A.; Nair, Mohandas; Hegde, Anaita Udwadia; Kumar, M. Pradeep; Sundaram, Soumya; Tilak, Preetha; Puri, Ratna D.; Shah, Krati; Sheth, Jayesh; Hasan, Qurratulain; Sheth, Frenny; Agrawal, Pooja; Katragadda, Shanmukh; Veeramachaneni, Vamsi; Chandru, Vijay; Hariharan, Ramesh; Mannan, Ashraf U.
Source
Journal of Neurology. 266(8):1919-1926
Subject
Language
English
ISSN
0340-5354
1432-1459
1432-1459
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.