What does this research mean for the field?

The extraocular muscle impairment in congenital myopathy caused by compound heterozygous Ryr1 mutations results from a complex combination of reduced calcium release units, disorganized muscle ultrastructure, and an unexpected loss of the ocular-muscle-specific myosin heavy chain-EO isoform. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

March 31, 2020Human Molecular Genetics

Molecular basis of impaired extraocular muscle function in a mouse model of congenital myopathy due to compound heterozygous Ryr1 mutations

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Why the study?

Recessive RYR1 mutations frequently cause severe congenital myopathies with ptosis and ophthalmoplegia, but the mechanisms underlying extraocular muscle involvement remained unclear.

Population

Knock-in mouse models of Ryr1 mutations

Comparison

Compound heterozygous RyR1p.Q1970fsX16+p.A4329D vs wild-type, single heterozygous, or homozygous RyR1p.A4329D mice

Design

Ex vivo animal experimental study

Authors

JEJan EckhardtFriedrich Miescher Institute CBChristoph BachmannUniversity of Basel SBSofia BenucciUniversity Hospital of Basel

Discussion

Member takes

Implication

Compound heterozygous RYR1 mutations may underlie ophthalmoplegia in congenital myopathy; leaves open translation from mouse models to patients.

Structured PICO

Population

Mouse models knocked-in for Ryr1 mutations (compound heterozygous RyR1p.Q1970fsX16+p.A4329D mutant mice)

Intervention

Compound heterozygous RyR1p.Q1970fsX16+p.A4329D mutations

Comparator

Wild-type, single heterozygous mutant carriers, or homozygous RyR1p.A4329D mice

Outcome

Ex vivo force production in extraocular muscles (EOMs)surrogate

Compound heterozygous Ryr1 mutations impair extraocular muscle function through direct effects on calcium release and indirect effects on myosin heavy chain isoform expression.

Cite This Study

Eckhardt et al. (2020) studied this question.

synapsesocial.com/papers/6a1dff98c238e2f4583521cc https://doi.org/10.1093/hmg/ddaa056

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March 31, 2020Human Molecular Genetics

Molecular basis of impaired extraocular muscle function in a mouse model of congenital myopathy due to compound heterozygous Ryr1 mutations

View Full Paper

Ask AI

Bookmark

Why the study?

Recessive RYR1 mutations frequently cause severe congenital myopathies with ptosis and ophthalmoplegia, but the mechanisms underlying extraocular muscle involvement remained unclear.

Population

Knock-in mouse models of Ryr1 mutations

Comparison

Compound heterozygous RyR1p.Q1970fsX16+p.A4329D vs wild-type, single heterozygous, or homozygous RyR1p.A4329D mice

Design

Ex vivo animal experimental study

Authors

JEJan EckhardtFriedrich Miescher Institute CBChristoph BachmannUniversity of Basel SBSofia BenucciUniversity Hospital of Basel

Discussion

Member takes

Implication

Compound heterozygous RYR1 mutations may underlie ophthalmoplegia in congenital myopathy; leaves open translation from mouse models to patients.

Structured PICO

Population

Mouse models knocked-in for Ryr1 mutations (compound heterozygous RyR1p.Q1970fsX16+p.A4329D mutant mice)

Intervention

Compound heterozygous RyR1p.Q1970fsX16+p.A4329D mutations

Comparator

Wild-type, single heterozygous mutant carriers, or homozygous RyR1p.A4329D mice

Outcome

Ex vivo force production in extraocular muscles (EOMs)surrogate

Compound heterozygous Ryr1 mutations impair extraocular muscle function through direct effects on calcium release and indirect effects on myosin heavy chain isoform expression.

Cite This Study

Eckhardt et al. (2020) studied this question.

synapsesocial.com/papers/6a1dff98c238e2f4583521cc https://doi.org/10.1093/hmg/ddaa056

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

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