Genetic identification of pathogenic variations of the DMD gene: a retrospective study from 10,481 neonatal patients based on next-generation sequencing data

Background An elevated level of creatine kinase (CK) is usually the primary screening marker for Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD). This study investigated the clinical application of next-generation sequencing (NGS) in newborns with a possible diagnosis of DMD/BMD in the neonatal intensive care unit (NICU). Methods NGS data from the NICU between June 1, 2016, and June 30, 2020, were reanalyzed by an in-house pipeline. Other methods confirmed the genetic findings, and clinical follow-up was performed until August 1, 2020. Results Of the 10,481 newborns, 19 (0.18%, 19/10,481) cases with pathogenic variations of the DMD gene were identified, including 13 (68.4%, 13/19) deletions, 4 (21.1%, 4/19) duplications, and 2 (10.5%, 2/19) nonsense mutations. Eight of the cases were diagnosed with DMD. Therapeutic strategies were modified for these patients. Six cases were diagnosed with BMD. Five patients except for 1 deceased patient were further followed-up, and clinical management was adjusted based on the clinical symptoms. The remaining 5 cases were indeterminate for DMD and BMD. Genetic counseling and further follow-up were performed or suggested. Conclusions Our study showed that DMD/BMD could be diagnosed earlier in the neonatal stage before the typical clinical symptoms appear. Early diagnosis may provide an opportunity for guiding the care and treatment of patients. However, ethical issues need to be kept in mind in the process of genetic counseling.