Analyze the type of mutation in the DMD The gene combined with motor milestone assessment may help better distinguish Duchenne muscular dystrophy (DMD) from Becker muscular dystrophy (BMD) in early life, a study has found.
Combining the two approaches had better predictive power than using either alone, and could mean children can receive targeted treatment sooner.
The results “significantly improved the rate of early diagnosis of DMD and provided a new tool for earlier diagnosis,” the researchers wrote, adding, “Both of these indicators are stable, easy to obtain, and have the potential to be widely promoted in the future. ”
The study, “Walking alone milestone combined reading frame rule improves early prediction of Duchenne muscular dystrophywas published in Frontiers in Pediatrics.
Mutations in the DMD are responsible for both DMD and BMD and in most cases are caused by deletion or duplication of DNA segments. Duchenne-associated mutations result in complete absence of the dystrophin protein and more severe disease presentation compared to Becker, resulting in either lower amounts of active dystrophin protein or dysfunctional protein and milder symptoms.
It is essential to distinguish between the two from the outset to ensure access to the right treatments. “Early intervention is essential, but early identification of DMD/BMD is the first step,” the researchers wrote.
The reading frame rule is a way to predict whether a DMD mutation will be associated with Duchenne or Becker. Essentially, it determines whether or not a mutation disrupts the DNA code reading frame.
The building blocks of DNA, called nucleotides, are “read” in groups of three during protein production. If a mutation disturbs this reading frame, it is called an out-of-frame mutation. This type of mutation usually means that the protein cannot be produced at all, resulting in DMD. But if a mutation is “in frame” and these trios can still be played, but with some changes, functional dystrophin can still be produced, although it is probably shorter than normal. This is associated with BMD.
But the rule is not infallible and some cases cannot be distinguished in this way.
Combining approaches for a better diagnosis
Children with DMD exhibit delays in certain motor steps, such as walking, crawling, or sitting, raising the possibility that these steps may be used to distinguish DMD from BMD early in life.
Researchers in China assessed whether using the reading frame rule and walking milestones together might have better predictive power than relying on just one.
The study included 152 boys diagnosed with DMD and 17 with BMD at Zhengzhou University-affiliated Children’s Hospital from 2014 to 2021. Those who lost the ability to walk and required a wheelchair to age 16 met the diagnostic criteria for DMD, while those who were still able to walk at age 16 were diagnosed with DMO.
The average age of onset of DMD was 3.9 years, with an age at diagnosis of 6.8 years. The age of onset of BMD was 6.5 years and that of diagnosis 7.1 years. Boys with DMD had significantly higher blood levels of creatine kinase, a marker of muscle damage.
Participants’ data was retrospectively assessed to determine whether each had reached the walking alone milestone, defined as the ability to walk alone by the age of 18 months (one and a half years).
The mean age of independent walking was 12.9 months, or just over a year, for BMD boys, and 18.0 months for DMD boys – a significant difference between the two groups. All boys in the DMD group reached the walking milestone alone, while 93 boys with DMD (61.2%) did not.
Genetic analyzes revealed that a DNA deletion was responsible for most of the DMD and BMD cases, accounting for the 17 DMD cases and the 136 DMD cases. The other cases of DMD were caused by DNA duplication. A majority of boys with BMD (12 out of 17) had an in-frame mutation, while a large majority of patients with DMD – 132 out of 152 – had an out-of-frame mutation. This means that 85.2% of cases complied with the reading frame rule.
Of all the deletion cases, the most common were deletions in a single exon (28.1%) – the bits of DNA that contain information for making proteins. A total of 106 cases (69.3%) had six or fewer exon deletions.
“Although reading frame helps predict the severity of skeletal muscle weakness, there is still some…variability in the prediction,” the researchers wrote. “Therefore, we combined the Reading Frame Ruler and the Gross Motor Milestone.”
The combined use of the reading frame rule and walking step alone had better predictive power for a diagnosis of DMD compared to BMD than either approach alone. Together they had a diagnosis rate of 93.49%, compared to 85.2% with the reading frame rule alone and 60.09% with walking alone.
“We believe that the combined index of the above two variables could have potential application for the early prediction of DMD,” the researchers wrote, noting that both approaches are easy for physicians to obtain and are not not expensive. The researchers said further studies with larger samples and in more regions would help verify their findings.
#Diagnosis #DMD #BMD #aided #genetics #milestones #Muscle..