RESUMEN
Genotypic definition of monogenic inborn errors of immunity (IEIs) continues to accelerate with broader access to next generation sequencing, underscoring this aggregated group of disorders as a major health burden impacting both civilian and military populations. At an estimated prevalence of 1 in 1200 individuals, IEIs affect ~8,000 patients within the Military Health System (MHS). Despite access to targeted gene/exome panels at military treatment facilities, most affected patients never receive a definitive genetic diagnosis that would significantly improve clinical care. To address this gap, we established the first registry of IEI patients within the MHS with the goal of identifying known and novel pathogenic genetic defects to increase diagnosis rates and enhance clinical care. Using the registry, a research protocol was opened in July 2022. Since July we have enrolled 75 IEI patients encompassing a breadth of phenotypes including severe and recurrent infections, bone marrow failure, autoimmunity/autoinflammation, atopic disease, and malignancy. Enrolled patients provide blood and bone marrow samples for whole genome, ultra-deep targeted panel and comprehensive transcriptome sequencing, plus cryopreservation of peripheral blood mononuclear cells for future functional studies. We are also implementing and developing analytical methods for identifying and interrogating non-coding and structural variants. Suspected pathogenic variants are adjudicated by a clinical molecular geneticist using state-of-the-art analysis pipelines. These analyses subsequently inform in vitro experiments to validate causative mutations using cell reporter systems and primary patient cells. Clinical variant validation and return of genetic results are planned with genetic counseling provided. As a proof of principle, this integrated genetic evaluation pipeline revealed a novel, candidate TLR7 nonsense variant in two adolescent brothers who both endured critical COVID-19 pneumonia, requiring mechanical ventilation and extracorporeal membrane oxygenation. Our protocol is therefore poised to greatly enrich clinical genetics resources available in the MHS for IEI patients, contributing to better diagnosis rates, informed family counseling, and targeted treatments that collectively improve the health and readiness of the military community. Moreover, our efforts should yield new mechanistic insights on immune pathogenesis for a broad variety of known and novel IEIs.Copyright © 2023 Elsevier Inc.
RESUMEN
Given the limited access to the healthcare services in India and the vulnerabilities therein, the physical well-being of the people in India is a matter of grave concern as is in other developing economies in the world. Though there has been advent of improvements in medical sciences and novel technological innovations therein, yet the reach of the same to the masses is questionable. Statistics indicate that there has been an increase in the people falling at a higher age bracket, all throughout the world. In India, the rural population embracing almost 6,40,000 villages have an unfortunate tale to narrate with more than 11% having no admittance to any sort of healthcare facilities. With the outbreak of Covid-19 and the subsequent need for far reaching screening to contain the same, there are new challenges of outreach constraints in densely populated countries like India. What further poses grave concern is the rural urban divide in the availability of healthcare amenities. All this calls for a progressive transformation and integration of medical sciences with information technology. The divide can be lessened with the aid of telehealth monitoring systems using IOT. In countries like India, where there is little access to doctors and medical infrastructure, such system would be an apt solution for interaction between the patients and the medical practitioners. Most of the villages in India are deprived of even rudimentary Public Health Centers, thus making it difficult for the resident villagers to receive even preliminary treatment. The telehealth monitoring system comes to rescue in such apathetic situations where it facilitates monitoring and measuring the physical vitals like pulse, levels of oxygen in the blood, rate of breath, glucose levels, temperature, lung capacity, ECG, and so on. The information so collected is stored in the cloud database which is then evaluated by the doctors and would eventually lead to generating prescriptions for the same and any other intervention as may be needed including emergency and EMRI services. The said project has created a website www.sfpieee.in which would help in dissemination of the information to be used by the physician. Under the call for proposals for combating Covid-19, with the support received from IEEE SIGHT/HAC and the Unnat Bharath Abhiyaan (UBA), this project has been conceptualized, designed, and implemented in Taramatipet Village of Telangana State. © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG.