Background : Rare diseases are a diverse set of disorders that individually affect a relatively small number of individuals but collectively form an important public health problem globally and in India. These diseases are often complex and challenging to diagnose and treat, significantly impacting lives of those affected and their families. Limitation in the knowledge that persists for most rare diseases is due to the dearth of reliable data on rare diseases in India. A patient registry is a powerful tool for systematically collecting data and creating a database necessary for informing healthcare policy and its execution. The National Registry for Rare and Other Inherited Disorders (NRROID) is a prospective hospital-based study initiated by the Indian Council of Medical Research in 2019 currently at 23 centres in India, to gather comprehensive data on selected rare diseases, including natural history, treatment, and disease outcomes, and to create a database to support further research and assist in the development of policies aimed at improving healthcare outcomes for rare disease patients. Currently, six broad groups of disorders, namely, storage disorders, inborn errors of metabolism (small molecule), skeletal dysplasias, primary immunodeficiencies, neuromuscular disorders, and hematological disorders have been included for reporting in the registry. Presently, NRROID provides valuable data related to demography, clinical features, diagnosis, management, and some other aspects of rare diseases. Results : Till February 2025, registry enrolled 15,369 patients under the 6 broad rare disease groups encompassing 231 rare diseases. Regional distribution depicts that the highest number of rare disease patients enrolled are from North India (34%) followed by South India (29%). Neuromuscular disorders (6307) account for the highest number of patient enrollments, followed by Thalassemia (3276) and Storage disorders (1632). A significant predominance of male patients (75%) has been reported in the registry, and the majority of patients (81.15%) fall in the pediatric age group under 18 years of age. Conclusion : This article summarizes the implementation of India’s first national rare disease registry and highlights key demographic and clinical trends. The NRROID provides foundational data to inform policy, research, and clinical care for rare disease patients in India.

Duchenne muscular dystrophy (DMD) is a severe genetic disorder characterized by progressive muscle degeneration, primarily affecting young males. In this study, we investigated arginine-modified hydroxyapatite nanoparticles (R-HAp) as a novel non-viral vector for DMD gene therapy, particularly for delivering the large 18.8 kb dystrophin gene. Addressing the limitations of traditional adeno-associated viral vectors, R-HAp demonstrated efficient binding and delivery of the dystrophin plasmid to DMD patient-derived skeletal muscle cells. Using confocal imaging and RT-PCR analysis, our results showed effective gene delivery and expression in both mouse myotubes and patient-derived cells, with sustained expression evident up to 5 days post transfection. The patient-derived myotubes also showed dystrophin protein production 7 days post transfection. These findings suggest R-HAp nanoparticles as a promising and cost-effective alternative for DMD treatment, highlighting their potential for overcoming current gene therapy challenges.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder with defect in dystrophin gene that shows features of degeneration of muscle tissue at an early age. Here, we describe iPSC lines generated from LCL of two patients of Indian origin carrying 46–48 and 49–50 exons deletions in DMD. The resulting iPSC lines IGIBi006-A and IGIBi008-A showed all the characteristic features of pluripotency, differentiated into cells of three germ layers in vitro and have no major genetic alterations due to reprogramming process. These lines can serve as a useful cell model for studying disease pathogenesis and will aid in precision therapy.

Abstract Background Duchenne muscular dystrophy (DMD) is an X‐linked recessive neuromuscular disorder characterised by progressive irreversible muscle weakness, primarily of the skeletal and the cardiac muscles. DMD is characterised by mutations in the dystrophin gene, resulting in the absence or sparse quantities of dystrophin protein. A precise and timely molecular detection of DMD mutations encourages interventions such as carrier genetic counselling and in undertaking therapeutic measures for the DMD patients. Results In this study, we developed a 2.1 Mb custom DMD gene panel that spans the entire DMD gene, including the exons and introns. The panel also includes the probes against 80 additional genes known to be mutated in other muscular dystrophies. This custom DMD gene panel was used to identify single nucleotide variants (SNVs) and large deletions with precise breakpoints in 77 samples that included 24 DMD patients and their matrilineage across four generations. We used this panel to evaluate the inheritance pattern of DMD mutations in maternal subjects representing 24 DMD patients. Conclusion Here we report our observations on the inheritance pattern of DMD gene mutations in matrilineage samples across four generations. Additionally, our data suggest that the DMD gene panel designed by us can be routinely used as a single genetic test to identify all DMD gene variants in DMD patients and the carrier mothers.

Background & objectives:Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder and is caused mainly by deletion, duplication and point mutations in the DMD gene. Diagnosis of DMD has been a challenge as the mutations in the.DMD:gene are heterogeneous and require more than one diagnostic strategy for the validation of the mutation. This study was planned to evaluate the targeted next-generation sequencing (NGS) as a single platform to detect all types of mutations in the DMD gene, thereby reducing the time and costs compared to conventional sequential testing and also provide precise genetic information for emerging gene therapies.Methods:The study included 20 unrelated families and 22 patients from an Indian population who were screened for DMD based on phenotypes such as scoliosis, toe walking and loss of ambulation. Peripheral blood DNA was isolated and subjected to multiplex ligation-dependent probe amplification (MLPA) and targeted NGS of the DMD gene to identify the nature of the mutation.Results:In the study patients, 77 per cent of large deletion mutations and 23 per cent single-nucleotide variations (SNVs) were identified. Novel mutations were also identified along with reported deletions, point mutations and partial deletions within the exon of the DMD gene.Interpretation & conclusions:Our findings showed the importance of NGS in the routine diagnostic practice in the identification of DMD mutations over sequential testing. It may be used as a single-point diagnostic strategy irrespective of the mutation type, thereby reducing the turnaround time and cost for multiple diagnostic tests such as MLPA and Sanger sequencing. Though MLPA is a sensitive technique and is the first line of a diagnostic test, the targeted NGS of the DMD gene may have an advantage of having a single diagnostic test. A study on a larger number of patients is needed to highlight NGS as a single, comprehensive platform for the diagnosis of DMD.