Life Sciences & Biotechnology
Title : | Deciphering the genomic landscape of Congenital Myasthenic Syndrome in India: A comprehensive phenotyping and functional enquiry into the pathogenetics |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Prof. Atchayaram Nalini, National Institute Of Mental Health And Neurosciences, Uttar Pradesh |
Timeline Start Year : | 2022 |
Timeline End Year : | 2025 |
Contact info : | atchayaramnalini@yahoo.co.in |
Details
Executive Summary : | The Congenital myasthenic syndromes [CMS] are diverse group of inherited disorders caused by impaired signal transmission at motor endplate that arise due to defects in single or multiple proteins. The safety margin of neuromuscular transmission is impaired due to functional or structural defects at neuromuscular junction. Although described in 1937 Congenital myasthenic syndromes were not distinguished as a separate entity until the autoimmune origin of myasthenia gravis [MG] and of the Lambert-Eaton myasthenic syndromes had been established. Advent of newer sequencing technologies has helped to unravel more genes responsible for disease causation than the traditional candidate gene association studies or linkage studies. The genes implicated in CMS have varied pathogenic mechanisms, clinical presentations and prognostic implications, thereby requiring different therapies. Even though CMS are genetic disorders with Mendelian inheritance pattern, they are potentially treatable. It is also noted that therapy benefiting one sub type of CMS can be ineffective or harmful in another type. Though some of the clinical presentations appear specific to an aberrant gene, significant phenotypic overlap does exist between the genes. Further there is significant intra and interfamilial variability suggesting modifier effect. Hence it is essential to establish a diagnosis at the genetic level for better tailor made therapeutics. Further genomic landscape of CMS in India is largely unknown apart from few small studies. Hence in this study we will attempt to subclassify 75 cases of CMS on clinical and electrophysiological findings. Later targeted exome and Whole exome sequencing [WES] where requiredwill be carried out to identify the underlying genetic cause of the syndrome and to perform genotype phenotype correlations. Through functional studies the effect of novel variantson gene expression, gene-gene interactions, protein content and protein localization will be studied using the affected muscle tissue. The effect of variants in ion channels on channel kinetics will also be studied. This comprehensive phenotyping technique will not only help in promoting individualized treatment but also in exploring newer pathogenetic mechanisms which mayhelp in identifying novel targets for newer drugs. |
Co-PI: | Dr. Saraswati Nashi, National Institute Of Mental Health And Neurosciences, Bangalore, Karnataka-560029, Dr. Seena Vengalil, National Institute Of Mental Health And Neurosciences, Bangalore, Karnataka-560029, Dr. Gautham Arunachal Udupi, National Institute Of Mental Health And Neurosciences, Bangalore, Karnataka-560029, Dr. Yogananda Shamamandri Markandeya, National Institute Of Mental Health And Neurosciences, Bangalore, Karnataka-560029, Dr. Chetan G K, National Institute Of Mental Health And Neurosciences, Bangalore, Karnataka-560029 |
Total Budget (INR): | 57,01,542 |
Organizations involved