Five Cases of Disorders of Sex Development in the Era of Next-generation Sequencing: Utility of Molecular Testing

Abstract Background: Genetic diagnosis of DSD (Disorders of Sex Development) is a challenge as it is a heterogeneous group of conditions. The availability of next-generation sequencing (NGS) has made the genetic diagnosis of these disorders easy. Objectives: This study describes the clinical, biochemical, and molecular characteristics of five cases of 46, XY DSD. Materials and Methods: Data of clinical, biochemical and molecular characteristics of five cases of 46, XY, DSD were collected retrospectively. Results: Out of the 5 cases, three had variants in the AR gene and one each had variants in the NR5A1 and DHX37 gene respectively. All five variants were pathogenic/likely pathogenic missense variants and two were novel variants. Conclusion: This study shows the genotypic and phenotypic heterogeneity of DSDs and the value of NGS-based testing in the diagnosis and management of DSD. NGS-based testing should be incorporated in the first-tier testing of DSDs. This study also highlights the challenges and complexities in the management of DSD including gender disclosure and sex of rearing.