Detection of a new pathogenic mutation on DMD gene associated with Duchene Muscular Dystrophy

Background and Aim : Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy and usually presents in early childhood with delayed milestones, including delays in sitting and standing independently. DMD is rapidly progressive, with affected children being wheelchair dependent by the age of 13 years. This disorder followed an X-linked recessive pattern and around 70% of cases are inherited from patients mother, however, about 30% of cases are the result of a new mutation. The current study evaluates a patient with a new pathogenic mutation on DMD gene which is associated with Duchene muscular dystrophy.Methods : The study is including an 11-year-old symptomatic boy with a significantly elevated level of CPK (Creatine phosphokinase) referred to the Dr. Mohaddes Medical Genetics Laboratory (DMMGL). Electromyogram (EMG) test showed the myogenic process and possible muscular dystrophy. His symptoms started at the age of 7 and he has been wheelchair dependent at the age of 9. Blood Sample was collected from the patient and the genetic sequencing test is performed using a custom-designed Nimblegen chip capturing the 79 associated genes with Duchene muscular dystrophy followed by Next Generation Sequencing. Detected variations were then validated using targeted Sanger sequencing.Results : One mutation c.4996C> T(p.Arg1666Ter; Hemi) on the DMD gene has been detected in hemizygous status. Although this mutation has been reported previously, its frequencies in the normal population are very low. The point mutation leads to alteration in the sequence of amino acids, which is expected to affect the protein’s function. Duchene muscular dystrophy (DMD) is inherited in an X-linked recessive manner. We detected this mutation in patient’s parents in heterozygous status.Conclusion : The c.4996C> T(p.Arg1666Ter; Hemi) mutation on the DMD gene has a pathogenic effect on dystrophin protein structure.

Keywords:

Duchenne muscular dystrophy (DMD) , DMD gene , Dystrophin , Pathogenic mutation , Next Generation Sequencing (NGS)