Rare diseases are progressive, chronically debilitating and/or life-threatening clinical conditions that have not received adequate attention in terms of diagnosis, research and treatment. Of the 350 million global estimate of patients, India alone is home to approximately 70 million (1 in 20) patients with known rare diseases. In addition, there are likely to be a large number of patients of rare disorders with unexplained genetic basis. Estimates for genetic disorders show that ~5 lakh infants with congenital malformations, ~4 lakh with G6PD deficiency and ~10,000 with amino acid disorders are born each year in our country. Biological isolation of several endogamous population groups may have resulted in a relatively higher prevalence of genetic disorders in India.

CDFD has been at the forefront of genetic diagnostics research and services for the past two and half decades. Taking our expertise forward, we now propose to develop an expanded program spanning diagnostics, research and counseling for “Pediatric rare genetic disorders”. We will use telemedicine to recruit patients with undiagnosed genetic diseases through a network of medical colleges (Pediatric Departments), DBT-UMMID centres, and 15 collaborating centres across the country.

We aim to analyse a total of 5600 families (1400 patient-parent trios for exome and 200 trios for genome sequencing per year) over 5 years to identify the genetic cause of undiagnosed pediatric rare genetic diseases. The objectives of this mission program will be achieved through a multi-faceted approaches including high-throughput whole exome (WES)/genome sequencing (WGS), analysis of sequence data, functional validation of the new genes/variants, and development of a database of phenotype-genotype. Results obtained from these studies will be provided to the patients/families along with appropriate genetic counseling. In addition, we plan to develop novel and affordable methods for diagnostics and screening of rare genetic diseases.. One of the collaborating centres (CMC, Vellore) will be working on development of novel therapeutic strategy for rare disorders.

The results obtained from this project will lead to more efficient diagnosis and genetic counselling of families suffering from inherited syndromes. The database of sequence variations along with phenotype of Indian pediatric patients will be of great value to genetic diagnostics laboratories within and outside India. The capacity built and resources developed during the course of this project will serve as a platform to facilitate similar studies in India. This mission programme will positively contribute towards Government of India’s Sustainable Development Goals regarding human health, and the objectives of the National Health Mission to mitigate the societal burden of genetic diseases.