Application whole exome sequencing for the clinical molecular diagnosis of patients with Duchenne muscular dystrophy; identification of four novel nonsense mutations in four unrelated Chinese DMD patients.

backgroundDuchenne muscular dystrophy (DMD) is the most common form of inherited muscular dystrophy. Germline mutations in dystrophin (DMD) gene cause DMD, with a X-linked recessive mode of inheritance. Patients with DMD are usually characterized by weakness of muscle, usually started since childhood and gradually the patient will unable to stand and walk.

methodsIn our present study, we identified four unrelated Chinese patients with DMD from four Chinese families. Whole exome sequencing was performed for genetic molecular analysis for these probands.

resultsWhole exome sequencing and confirmatory Sanger sequencing identified four novel nonsense mutations in these four unrelated Chinese patients, respectively. All these four mutations lead to the formation of a truncated DMD protein by formation of a premature stop codon. According to the variant interpretation guidelines of American College of Medical Genetics and Genomics (ACMG), these four novel nonsense mutations are categorized as "likely pathogenic" variants.

conclusionOur present finding not only identified four novel loss-of-function mutations in dystrophin (DMD) gene but also strongly emphasized the significance of whole exome sequencing as the most efficient way of identifying the candidate genes and mutations which enables us for easy and rapid clinical diagnosis, follow-up, and management of DMD patients.