Emery-Dreifuss Muscular Dystrophy Type 1 in a 15-Year-Old Patient Due to a Novel Putative Splice-Site Mutation

Background: Three months before the initial presentation, a 15-year-old male patient developed toe-walking bilaterally without any relevant muscle weakness. An elevation of serum creatine kinase in the range of ~1,000 U/L could be shown on several occasions. A motor nerve conduction study as well as a whole body muscle MRI were performed and yielded unremarkable results. After an abnormal 12-lead resting ECG, 24-hour Holter ECG monitoring showed constant atrial flutter. Thus, in view of the combination of the patient’s symptoms, Emery-Dreifuss muscular dystrophy had to be suspected.

Methods: Sequencing of genes responsible for an Emery-Dreifuss phenotype was performed via high throughput sequencing on a HiSEq. 2,500/4,000 platform. In addition, the patient underwent a skin biopsy for immunohistochemical analysis with an anti-Emerin antibody. We plan to compare the wildtype cDNA of the EMD gene to the EMD-cDNA of our patient after RNA stabilization in a PAXGene tube and RT-PCR.

Results: A novel, hemizygous mutation in the EMD gene (c.82G>A; p.Gly28Arg) was identified. Due to the localization of the mutation in the last nucleotide of the first exon, aberrant splicing had to be postulated. Immunohistochemistry showed complete loss of Emerin expression in the skin biopsy, proving the pathogenicity of the identified mutation. cDNA analysis will be performed to verify the splice effect of the EMD mutation.

Conclusion: In case cardiac symptoms, elevation of the creatine kinase and slight contractures are present, Emery-Dreifuss muscular dystrophy should be considered as a differential diagnosis. In our patient a novel mutation in the EMD gene was discovered, leading to a complete loss of Emerin expression via a putative splice effect.