Rare diseases are those diseases that are not seen frequently in a population. There are about 7000 rare diseases that have been identified worldwide, and 80% of them are caused by genetic changes. Since a small number of individuals are affected with rare diseases, most clinicians are not aware of such diseases, and thus, they remain undiagnosed and untreated. Awareness regarding such diseases is essential to train clinicians to diagnose individuals affected with these disorders and to develop National/International Registries, which will serve to give information about the disease prevalence, its natural course, treatment, and management options available, to the medical fraternity. Patient advocacy groups play a remarkable and unique role in forming the collective voice of individuals living with rare diseases. They help in the identification, diagnosis, management, treatment, and prevention of such diseases. Advocacy Groups form collaborative partnerships with scientists studying such rare diseases, clinicians managing these diseases, pharmaceutical companies developing drugs, and Government officials overseeing and policy makers implementing medical regulatory processes. Thus, advocacy groups play a key role in helping patients and families with rare diseases.

Background Disorders involving the musculoskeletal system are often identified with short stature and a range of orthopedic problems. The clinical and genetic heterogeneity of these diseases along with several characteristic overlaps makes definitive diagnosis difficult for clinicians. Hence, using molecular testing in addition to conventional tests becomes essential for appropriate diagnosis and management. Methods Comprehensive clinical examination, detailed pretest and posttest counseling, molecular diagnosis with next-generation sequencing (NGS), genotype–phenotype correlation and Sanger sequencing for targeted variant analysis. Results This manuscript reports a molecular spectrum of variants in 34 orthopedic cases referred to a single genetic unit attached to a tertiary care hospital. The diagnostic yield of NGS-based tests coupled with genetic counseling and segregation analysis was 79% which included 7 novel variants. In about 53% (i.e. 18/34 cases), molecular testing outcome was actionable since 8 of the 18 underwent prenatal diagnosis, as they were either in their early gestation or had planned a pregnancy subsequent to molecular testing, while ten cases were premaritally/prenatally counseled for the families to take informed decisions as they were in the reproductive age. Conclusions The report highlights the importance of NGS-based tests even in a low resource setting as it helps patients, families and healthcare providers in reducing the economic, social and emotional burden of these disorders.

The twin image-free phase reconstruction is still a challenge with single-shot inline holographic systems. Existing solutions mostly are based on the inverse problem approaches or alternating projections. However, there exists a trade-off between phase retrieval and twin image elimination. Recent studies have introduced a hybrid method involving both the approaches to mitigate this trade-off. Following these works, we propose a single-shot sparsity-assisted iterative phase retrieval approach that applies a sparsity constraint in the object domain and formulates phase retrieval as a minimization problem. We demonstrate lensless digital inline holographic microscopy for imaging transparent and weakly scattering biological samples over a large field-of-view of [Formula: see text]. The proposed method achieves high fidelity phase reconstruction with faster convergence compared to the existing single-shot phase retrieval methods. We further demonstrate the phase quantification of label-free biological samples, such as cervical cells and RBCs, to highlight the potential of our technique in clinical applications.

Corona virus disease 2019 (COVID-19) has taken the world by storm with global infectivity and mortality of 3.5%. Since there is no specific treatment for COVID-19, several drugs have been repurposed to combat infection, these include drugs like anti-malarial – chloroquine, hydroxychloroquine, anti- diarrheal– loperamide and antipsychotic-promazine, which have been considered to be effective inhibitors as of viral binding to ACE2 receptor. The administration of these drugs is currently random and is the key factors responsible for varied treatment response, hence genes involved in drug metabolism should be analysed before planning therapy. Genes involved in metabolism of the listed drugs are ABCB1, CYP1A2, CYP2C8, CYP2C19, CYP3A4 and CYP2D6. Unpublished pharmacogenomic data from our internal cohort (75 cases) was analyzed to predict likely-responders and non-responders to propose drugs for COVID-19 drug therapy in our population. Preliminary data from random individuals without bias indicates that both anti-malarials at standard dose will benefit 98% of our cases (in absence of co-morbidities), while 11-85% of individuals would require dose reduction/alternatives for loperamide and promazine. Anti-malarials like chloroquine, hydroxychroloquine can be prescribed for prophylaxis and as first line of therapy in absence of comorbidities.  Simple genotype testing of ABCB1, CYP1A2, CYP2C19 and CYP2D6 is an indispensable tool to predict treatment outcomes of loperamide and promazine for COVID-19 patients.

Aim: Renal disorders (RDs) are heterogeneous in nature with different ages of onset ranging from in-utero to adults that arise as independent disease and also as syndromes. RDs are of both heritable and acquired type. The aim of this study was to utilize Next Generation Sequencing to identify the molecular basis of syndromic and non syndromic RDs for management and preventative counselling.Methods: In the present study cases of RDs which were identified as a solitary health issue and those which had renal disease as part of syndromic features were offered exome analysis by Next Generation Sequencing (NGS) followed by a specific gene panel evaluation after informed consent. Results: In our study twenty cases were evaluated by NGS based panel tests, a genetic variant was identified in 95% (19/20) of the cases which could be correlated with the renal phenotype. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines 89% (17/19) of the cases were reported with a Pathogenic or likely pathogenic variant and 10% (2/19) with a Variant of uncertain significance. As expected 8/9 cases with features of polycystic Kidney disease and all eleven cases with syndromic RD had a variant which correlated with phenotype.Discussion & Conclusion: NGS enables molecular diagnosis of RD without subjecting patients to invasive tests like renal biopsy as early as the fetal stage. The management and prevention of disease in the family through appropriate genetic counseling is an added advantage.