HNRNPA1 de novo Variant Associated with Early Childhood Onset, Rapidly Progressive Generalized Myopathy
Roos, Andreas | Häusler, Martin | Kollipara, Laxmikanth | Topf, Ana | Preusse, Corinna | Stucka, Rolf | Nolte, Kay | Strom, Tim | Berutti, Riccardo | Jiang, Xuehui | Koll, Randi | Lochmüller, Hanns | Schacht, Sabine Maria | Zahedi, René P. | Weis, Joachim | Senderek, Jan
HNRNPA1 variants are known to cause degenerative motoneuron and muscle diseases which manifests in middle age or later. We report on a girl with early childhood onset, rapidly progressive generalized myopathy including ultrastructural findings in line with a proteinopathy. Proteomics of patient-derived muscle and combined screening of genomic data for copy number variations identified a HNRNPA1 de novo intragenic deletion as causative for the phenotype. Our report expands the spectrum of HNRNPA1-related diseases towards early-childhood onset and adds HNRNPA1 to the growing list of ALS and myopathy genes for which certain mutations may cause severe pediatric phenotypes.