P.151 - ABSTRACT WITHDRAWN Myopathy caused by mutations in the HNRNPA1 gene

Abstract

We previously described an adult-onset distal myopathy (MPD3, OMIM #610099) in a large Finnish family with a dominant mode of inheritance. Small hand muscles (intrinsic, thenar and hypothenar) were first involved with spread to the lower legs and later proximal muscles. Dystrophic changes with rimmed vacuoles and cytoplasmic inclusions were observed in muscle biopsies at advanced stage. The causative variant was identified in the <i>HNRNPA1</i> gene. This was a heterozygous deletion of the DNA segment chr12:54677979-54678138 spanning the second last exon 10 of the gene. Whole RNA sequencing showed that the main RNA product of the mutant allele results from splicing of exon 9 to 11 and encodes the predicted protein p.Gly356Asnfs*4. Additional likely disease-causing <i>HNRNPA1</i> variants were identified in other families with compatible phenotypes. Functional characterization of p.Gly356Asnfs*4 and other novel variants in cell culture models is ongoing to characterize their effects on protein properties and on stress granule dynamics.