A new study published in Cureus has revealed that novel deleterious DMD exon 11 frameshift mutation variant and CAV3 single copy deletion coexist in patients with Duchenne muscular dystrophy (DMD), requiring patient-specific treatment modalities for alleviation of the disorder.
Inherited muscular dystrophies are a set of disorders resulting from the mutations in structural proteins linking intracellular actin to the extracellular matrix. These mutations occur in the actin-binding dystrophin protein or the extracellular protein-binding dystrophin-associated protein complex (DAPC), including various structural proteins such as caveolins.
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The study presented a case of a 9-year-old male child with a novel deleterious DMD exon 11 frameshift mutation variant and an accompanying heterozygous CAV3 single copy deletion. The patient was presented with a primary complaint of muscle weakness. He was reported to have a more classic DMD phenotype, consistent with DMD mutations that impair or eliminate the dystrophin protein’s expression.
The patient had a medical history significant for hypospadias with repair, sickle cell trait, and prematurity, with delivery at 31 weeks through a c-section for maternal eclampsia. Moreover, the patient met normal motor milestones through 2.5 years of age with no significant hospitalizations until 7 years of age, when he had difficulty walking endurance due to muscle weakness.
After the initial examination, the patient was reported to have shortened his heel cords bilaterally, so a walker was recommended. Moreover, he continued to experience rapid breathing and occasional fast heart rate during physical activity. He could not reach age-appropriate milestones for gross motor skills such as climbing stairs, hopping, and maintaining balance.
During the physical examination, the child displayed a playful, attentive, and interactive personality, and no abnormalities related to cranial nerves were detected. The musculoskeletal exam revealed a positive Gower sign, bilateral calf hypertrophy, shortened feet, and lumbar lordosis. Based on the clinical history, laboratory findings, and physical examination, the patient was diagnosed with DMD.
The study discussed the therapeutic approaches for this interesting case. The findings suggested that the patient’s case demonstrated that there might be potential therapeutic opportunities in using gene editing and other emerging technologies to correct the genetic defects underlying DMD and related disorders.
“With advancements in our genetic toolkit, we can expect patient-specific treatment modalities to emerge which would address specific mutations and lead to the alleviation of disorders,” the authors concluded.
Khan MW, Raza S, Raza M, et al. Coexistence of a heterozygous caveolin-3 deletion and a novel dystrophin gene mutation in a Duchenne muscular dystrophy patient. Cureus 2023. Published online February 6, 2023. doi: 10.7759/cureus.34704