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MATR3 – Vocal Cord and Pharyngeal Distal Myopathy (VCPDM)

Heterozygous variants in MATR3 underlie autosomal dominant vocal cord and pharyngeal distal myopathy (VCPDM). The c.254C>G (p.Ser85Cys) missense change was identified in one unrelated adult proband presenting with progressive, asymmetric distal muscle weakness, dysphonia, dysphagia, and respiratory insufficiency (1 proband (PMID:35812165)). No additional segregation has been reported. Functional evidence from transgenic mice expressing S85C MATR3 recapitulated myopathic changes including fiber-size variation, internal nuclei, rimmed vacuoles, limb weakness, and respiratory involvement (PMID:31056746).

Key Take-home: The MATR3 c.254C>G (p.Ser85Cys) variant should be considered in the diagnostic evaluation of autosomal dominant VCPDM.

References

  • Neurology. Genetics • 2022 • Expanding the Phenotypic Spectrum of Vocal Cord and Pharyngeal Weakness With Distal Myopathy due to the p.S85C MATR3 Mutation. PMID:35812165
  • The Journal of pathology • 2019 • A mutant MATR3 mouse model to explain multisystem proteinopathy. PMID:31056746

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Single unrelated proband with heterozygous c.254C>G (p.Ser85Cys) and characteristic VCPDM features ([PMID:35812165])

Genetic Evidence

Limited

One missense variant identified in a single patient, no segregation data ([PMID:35812165])

Functional Evidence

Moderate

Transgenic S85C MATR3 mice replicate myopathic and vocal cord weakness phenotype ([PMID:31056746])