Diagnosis and Management of Myotonic Dystrophy Type 1

Hartman, Julia; Patki, Tejal; Johnson, Nicholas E.

doi:10.1001/jama.2024.2511

Cited by 2 publications

(1 citation statement)

References 9 publications

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“…DM1 is inherited in an autosomal dominant manner and is caused by a CTG trinucleotide repeat expansion (CTG n ) in the 3' untranslated region of the dystrophia myotonica protein kinase (DMPK) gene [2][3][4] . Although nearly every organ system can be affected, the core clinical features of DM1 include progressive distal muscle weakness, early onset cataracts, and myotonia (i.e., delayed muscle relaxation following contraction) 5,6 .…”

Section: Introductionmentioning

confidence: 99%

RNA mis-splicing in children with myotonic dystrophy is associated with physical function

Hartman,

Ikegami,

Provenzano

et al. 2024

Preprint

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ObjectivesDysregulated 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.Methods82 participants (42 DM1 adults & 40 CDM children) 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]inferredin skeletal muscle biopsies. Multiple linear regression analysis was performed to predict [MBNL]inferredusing clinical outcome measures alone. Similar analyses were performed to predict 12-month physical function using baseline metrics.ResultsMyotonia (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]inferredin our cohort of all DM1 individuals and when assessing CDM children independently. Multiple linear regression analyses yielded two models capable of predicting [MBNL]inferredfrom select clinical outcome assessments alone in all subjects (adjusted R2= 0.6723) or exclusively in CDM children (adjusted R2= 0.5875).InterpretationOur findings establish significant correlations between skeletal muscle performance and a composite measure of alternative splicing dysregulation, [MBNL]inferred,in DM1. The strength of these correlations and the development of the predictive models will assist in designing efficacious clinical trials for individuals with DM1, particularly CDM.

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Section: Introductionmentioning

confidence: 99%

RNA mis-splicing in children with myotonic dystrophy is associated with physical function

Hartman,

Ikegami,

Provenzano

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

RNA mis‐splicing in children with congenital myotonic dystrophy is associated with physical function

Hartman,

Ikegami,

Provenzano

et al. 2024

Ann Clin Transl Neurol

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ObjectivesDysregulated 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.MethodsEighty‐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]inferred, in skeletal muscle biopsies. Multiple linear regression analysis was performed to predict [MBNL]inferred using clinical outcome measures alone. Similar analyses were performed to predict 12‐month physical function using baseline metrics.ResultsMyotonia (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]inferred 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]inferred from select clinical outcome assessments alone in all subjects (adjusted R2 = 0.6723) or exclusively in children with CDM (adjusted R2 = 0.5875).InterpretationOur findings establish significant correlations between skeletal muscle performance and a composite measure of alternative splicing dysregulation, [MBNL]inferred, 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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Diagnosis and Management of Myotonic Dystrophy Type 1

Abstract: This JAMA Insights discusses the signs and symptoms, diagnosis, and treatment of myotonic dystrophy type 1.

Cited by 2 publications

References 9 publications

RNA mis-splicing in children with myotonic dystrophy is associated with physical function

RNA mis-splicing in children with myotonic dystrophy is associated with physical function

RNA mis‐splicing in children with congenital myotonic dystrophy is associated with physical function

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