Utility of Next Generation Sequencing in Genetic Testing and Counseling of Disorders Involving the Musculoskeletal System–Trends Observed From a Single Genetic Unit

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, with several characteristic overlaps, makes specific diagnosis difficult for clinicians using conventional tests, hence molecular testing becomes essential for appropriate diagnosis and management. Methods: : Next Generation Sequencing (NGS) based testing has become common in current day clinical practice. To do genetic counseling in cases with disorders in musculoskeletal system, classify and refer for appropriate genetic testing and to assess utility of NGS based testing for molecular diagnosis . Detailed pre and posttest genetic counseling, NGS based clinical exome testing, genotype-phenotype correlation, and segregation 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. Cases which benefited or will get a benefit in the near future were 53% (i.e. 18/34 cases), as eight underwent prenatal diagnosis, since 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 health care providers in reducing the economic, social and emotional burden of these disorders.