A novel DMD splicing mutation found in a family responsible for X-linked dilated cardiomyopathy with hyper-CKemia

Area of Science:

• Genetics
• Cardiology
• Molecular Biology

Background:

• X-linked dilated cardiomyopathy (XLDC) is a severe cardiac condition often associated with muscle disorders.
• Identifying the genetic basis of XLDC is crucial for diagnosis and genetic counseling.
• Previous studies have linked XLDC to mutations in the dystrophin-glycoprotein complex.

Purpose of the Study:

• To detect a novel mutation responsible for X-linked dilated cardiomyopathy with hyper-CKemia.
• To investigate the genetic cause in a proband presenting with cardiac symptoms and elevated creatine kinase levels.

Main Methods:

• Clinical investigation including physical examination, laboratory tests, electromyography, echocardiography, and cardiac MRI.
• Muscle biopsy for histopathology and immunohistochemistry to assess sarcolemma changes.
• Next-generation sequencing and bioinformatics analysis for mutation detection, confirmed by Sanger sequencing in family members.

Main Results:

• Clinical findings confirmed dilated cardiomyopathy with hyper-CKemia but no skeletal muscle involvement.
• Histopathology revealed dystrophic changes, with reduced dystrophin-N and delta-sarcoglycan.
• A novel hemizygous splicing mutation (c.31+1G>C) in exon 1 of the DMD gene was identified in the patient and his nephew, with carrier status in his mother and sister.

Conclusions:

• A novel pathogenic mutation at the exon 1 splicing site of the DMD gene is responsible for X-linked dilated cardiomyopathy with hyper-CKemia.
• This finding expands the spectrum of DMD gene mutations and their clinical manifestations.
• Genetic testing and counseling are essential for families with this condition.