A Novel Mutation (Lys31Arg) in the DMD Gene Impacts on Neuromuscular Dysfunctions Found by Whole Exome Sequencing and

backgroundDuchene Muscular Disorder (DMD) is a severe X-linked recessive neuromuscular disease. Previous reports predicted that one-third of cases with a fatal X-linked recessive disease will be caused by a novel mutation, and the mutation rate for DMD seems to be higher in males.

objectiveA novel mutation in the DMD gene DMD (NM_004006.3):c.92A>G (p.Lys31Arg) is suggested for males because of their heterozygous mothers carrying the mutant alleles.

methodWhole Exome Sequencing (WES) was done for a 25-year-old female followed by the screening of the novel mutation in her parents and her brother by the Sanger sequencing technique. Some in silico analyses were run to find the putative alterations in wild-type and mutant structures by PolyPhen-2 and Mupro. Notably, SWISS-MODEL was performed to build a reliable model for the mutant allele based on the PDB ID: 1DXX structure. Also, superimposition was done by PyMol.

resultsWES analysis revealed three novel mutations including DLD (exon13:c.G1382A:p. G461E), ABCA3 (exon12:c.G1404C:p.W468C), and DMD (exon2:c.A92G:p.K31R) in the case. Focusing on DMD mutation, Sanger sequencing of the patient's parents and brother indicated no mutant allele in her mother and brother but a mutant allele in her father as a hemizygous pattern. In silico analyses showed no considerable change regarding pathogenic impact.

conclusionIn conclusion, our findings revealed no pathogenic effect of the new mutation (K31R) of the DMD gene in an Iranian 25-year-old woman. Because of the DMD importance in preclinical diagnosis, these data may shed a light on the diagnosis of this mutation in future pregnancies.