The incidence of children with inherited neurodevelopmental disorders (NDD) is high in low- and middle- income countries (LMIC) and becoming an enormous burden on heath care resources. While individual inherited NDD are rare, in aggregate they affect millions of people. Whole exome sequencing (WES) has risen to the forefront of genetic testing in High and Middle Income Countries (HMIC) based on its potential to uncover genetic causes for inherited NDD conditions, while circumventing bottlenecks caused by candidate gene screening approaches. Dr. Girisha at Kasturba Medical College at Manipal University, India and Dr. Bielas in the Department of Human Genetics at University of Michigan Medical School, US will build an ongoing collaboration to implement WES technology in the Department of Medical Genetics at Manipal University. This collaboration will upgrade the research capacity to support the use of WES for diagnosis of known causes of NDD. We will supplement education of medical genetics professionals and facilitate the incorporation of genetic counseling into genetic diagnoses. The World Health Organization recommends incorporating genetic counseling into the continuum of medical genetics care as it is predicted to lead to a reduction in the burden of NDD. The proposed infrastructure development will lay the foundation for future applications aimed at identifying novel genetic causes of NDD, developing research capacity to functionally test novel deleterious alleles and developing best practices for clinical application of WES in India.
This application proposes an Indo-US collaboration to establish genetic diagnostic tools in the Indian clinical setting to address inherited causes of neurodevelopmental disorders that are lethal or cause lifelong impairments. These resources will be available to patients across the socioeconomic spectrum. Pairing genetic counseling with genetic diagnoses is predicted to ameliorate the disease burden caused by inherited neurodevelopmental disorders.
| Galada, Chelna; Hebbar, Malavika; Lewis, Leslie et al. (2018) Report of four novel variants in ASNS causing asparagine synthetase deficiency and review of literature. Congenit Anom (Kyoto) 58:181-182 |
| Srivastava, Anshika; Srivastava, Kinshuk Raj; Hebbar, Malavika et al. (2018) Genetic diversity of NDUFV1-dependent mitochondrial complex I deficiency. Eur J Hum Genet 26:1582-1587 |
| Hebbar, Malavika; Kanthi, Anil; Shukla, Anju et al. (2018) A biallelic 36-bp insertion in PIBF1 is associated with Joubert syndrome. J Hum Genet 63:935-939 |
| Hebbar, Malavika; Shukla, Anju; Nampoothiri, Sheela et al. (2018) Locus and allelic heterogeneity in five families with hereditary spastic paraplegia. J Hum Genet : |
| Harms, Frederike Leonie; Girisha, Katta M; Hardigan, Andrew A et al. (2017) Mutations in EBF3 Disturb Transcriptional Profiles and Cause Intellectual Disability, Ataxia, and Facial Dysmorphism. Am J Hum Genet 100:117-127 |
| Srivastava, Anshika; McGrath, Brian; Bielas, Stephanie L (2017) Histone H2A Monoubiquitination in Neurodevelopmental Disorders. Trends Genet 33:566-578 |
| Nampoothiri, Sheela; Hebbar, Malavika; Roy, Arun Grace et al. (2017) Hyperphosphatasia with Mental Retardation Syndrome Due to a Novel Mutation in PGAP3. J Pediatr Genet 6:191-193 |
| Shukla, Anju; Upadhyai, Priyanka; Shah, Jhanvi et al. (2017) Autosomal recessive spinocerebellar ataxia 20: Report of a new patient and review of literature. Eur J Med Genet 60:118-123 |
| Hebbar, Malavika; Girisha, Katta M; Srivastava, Anshika et al. (2017) Homozygous c.359del variant in MGME1 is associated with early onset cerebellar ataxia. Eur J Med Genet 60:533-535 |
| Patil, Siddaramappa J; Somashekar, Puneeth H; Shukla, Anju et al. (2017) Clinical Variability in Familial X-Linked Ohdo Syndrome-Maat-Kievit-Brunner Type with MED12 Mutation. J Pediatr Genet 6:198-204 |
Showing the most recent 10 out of 12 publications
