Novel mutation in exon 56 of the dystrophin gene in a child with Duchenne muscular dystrophy

Abstract

Duchenne type muscular dystrophy (DMD) is an allelic X-linked recessive disorder caused by mutations in the gene encoding dystrophin. Genotype analysis has shown that deletion mutations account for approximately 65% of all cases, and 5-10% are duplications, while the remaining 30% of affected individuals may have smaller mutations, including point mutations, small deletions or small insertions. In this study, we present the case of a 4-year-old boy with typical clinical features of DMD, who developed normally until the age of 2. However, at age 3 he presented his first symptom, a tendency to fall, had difficulty in rising from the floor and in walking on his toes. At age 4 he had a waddling gait and could no longer climb stairs. A physical examination revealed proximal muscle weakness, calf hypertrophy, deep tendon hyporflexia and a positive Gower's sign. To identify the disease-causing gene in the proband, all coding regions (exons 1-79) of the dystrophin gene were PCR-amplified and sequenced. A novel duplication (c.8284dupA) in exon 56 of the dystrophin gene was identified, which was predicted to generate a frameshift mutation and create a premature termination codon (p.Ile2762Asnfs*10). This mutation was further confirmed by single-strand conformation polymorphism (SSCP) analysis, which revealed an extra band found in exon 56 of the dystrophin in the proband; however, this was not present in his family members or in the 100 matched normal controls. The data presented in this study may aid in expanding the spectrum of mutations causing DMD. To our knowledge, we demonstrate for the first time that a small duplication mutation can cause severe DMD.

A novel rabbit model of Duchenne muscular dystrophy generated by CRISPR/Cas9

“…It was also not feasible to perform grip strength measurement on these animals owing to their large body size. However, functional defects of skeletal muscle in the DMD KO rabbits were obviously detected by the reduced physical activity and impaired ability to climb up the step, very similar to DMD pigs ( Klymiuk et al, 2013 ) and boys with DMD in their early life ( Zhu et al, 2013 ) ( Table 3 ).…”

Novel heterozygous mutation c.4282G>T in the SCN5A gene in a family with Brugada syndrome

“…Direct DNA sequencing analyses. As described previously (21,22), venous blood (5 ml) was collected from the participants, and total human genomic DNA was purified with the DNA Isolation kit for Mammalian Blood (Roche Diagnostics, Indianapolis, IN, USA). Considering that SCN5A thus far remains the most frequently reported gene causing BrS, mutation screening of the SCN5A gene was carried out directly without performing linkage analysis.…”

Nanomedicine for Gene Delivery and Drug Repurposing in the Treatment of Muscular Dystrophies

“…Lack of dystrophin induces severe muscle weakness, inflammation and wasting, described as cardinal signs of DMD. Diverse mutations on DMD gene have been reported worldwide [55]. Over the years, DMD gene has been characterised, identifying which mutations lead to a severe DMD phenotype [56,57].…”