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Neurodevelopmental Disorder with Dystonia and Chorea Linked to De Novo Variants in the Splicing Regulator SRRM4 - PubMed

3 hours ago
  • #movement disorders
  • #neurogenetics
  • #RNA splicing
  • SRRM4 gene variants cause a neurodevelopmental disorder with dystonia and chorea in three patients.
  • De novo splice-site variants (c.464+2T>C, c.464+2T>A) lead to altered SRRM4 mRNA isoforms and abnormal splicing.
  • Clinical features include infantile onset of combined dystonic and choreatic syndromes or chorea-predominant disease.
  • Mechanism involves mis-splicing of downstream targets like AP1S2, not simple loss-of-function, suggesting therapeutic potential.