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

Ganapathy, Aparna and Mishra, Avshesh and Soni, Megha Rani and Kumar, Priyanka and Sadagopan, Mukunth and Kanthi, Anil Vittal and Patric, Irene Rosetta Pia and George, Sobha and Sridharan, Aparajit and Thyagarajan, T C and Aswathy, S L and Vidya, H K and Chinnappa, Swathi M and Nayanala, Swetha and Prakash, Manasa B and Raghavendrachar, Vijayashree G and Parulekar, Minothi and Gowda, Vykuntaraju K and Nampoothiri, Sheela and Menon, Ramshekhar N and Pachat, Divya and Udani, Vrajesh and Naik, Neeta and Kamate, Mahesh and Devi, A Radha Rama and Kunju, P A Mohammed and Nair, Mohandas and Hegde, Anaita Udwadia and Kumar, M. Pradeep and Sundaram, Soumya and Tilak, Preetha and Puri, Ratna D and Shah, Krati and Sheth, Jayesh and Hasan, Qurratulain and Sheth, Frenny and Agrawal, Pooja and Katragadda, Shanmukh and Veeramachaneni, Vamsi and Chandru, Vijay and Hariharanu, Ramesh and Manna, Ashraf U (2019) Multi-gene testing in neurological disorders showed an improved diagnostic yield: data from over 1000 Indian patients. In: JOURNAL OF NEUROLOGY, 266 (8). pp. 1919-1926.

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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.

Item Type:	Journal Article
Publication:	JOURNAL OF NEUROLOGY
Publisher:	SPRINGER HEIDELBERG
Additional Information:	copyright for this article belongs to SPRINGER HEIDELBERG
Keywords:	Neurological disorders; Genetic testing; Next-generation sequencing; Multi-gene panel
Department/Centre:	Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering Others
Date Deposited:	08 Aug 2019 09:14
Last Modified:	08 Aug 2019 09:14
URI:	http://eprints.iisc.ac.in/id/eprint/63355

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