AI Article Synopsis

  • The study investigates the link between RNA alternative splicing abnormalities and physical function in children with congenital myotonic dystrophy (CDM), a severe form of myotonic dystrophy type 1 (DM1).
  • Researchers analyzed data from 82 participants, including adults with DM1 and children with CDM, assessing muscle biopsies, motor function, strength, and myotonia.
  • Results showed a significant correlation between myotonia and RNA mis-splicing in all DM1 individuals, while motor performance and strength were associated with splicing dysregulation, aiding future clinical trial designs for DM1 and CDM.

Article Abstract

Objectives: Dysregulated RNA alternative splicing is the hallmark of myotonic dystrophy type 1 (DM1). However, the association between RNA mis-splicing and physical function in children with the most severe form of disease, congenital myotonic dystrophy (CDM), is unknown.

Methods: Eighty-two participants (42 adults with DM1 and 40 children with CDM) with muscle biopsies and measures of myotonia, motor function, and strength were combined from five observational studies. Data were normalized and correlated with an aggregate measure of alternative splicing dysregulation, [MBNL], in skeletal muscle biopsies. Multiple linear regression analysis was performed to predict [MBNL] using clinical outcome measures alone. Similar analyses were performed to predict 12-month physical function using baseline metrics.

Results: Myotonia (measured via vHOT) was significantly correlated with RNA mis-splicing in our cross-sectional population of all DM1 individuals; CDM participants alone displayed no myotonia despite a similar range of RNA mis-splicing. Measures of motor performance and muscle strength were significantly associated with [MBNL] in our cohort of all DM1 individuals and when assessing children with CDM independently. Multiple linear regression analyses yielded two models capable of predicting [MBNL] from select clinical outcome assessments alone in all subjects (adjusted R = 0.6723) or exclusively in children with CDM (adjusted R = 0.5875).

Interpretation: Our findings establish significant correlations between skeletal muscle performance and a composite measure of alternative splicing dysregulation, [MBNL], in DM1. The strength of these correlations and the development of predictive models will assist in designing efficacious clinical trials for individuals with DM1, particularly CDM.

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Source
http://dx.doi.org/10.1002/acn3.52224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651218PMC

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