An Alu mediated intergenic inversion in RBCK1 causing Polyglucosan body myopathy type 1

Polyglucosan body myopathy type 1 (PGBM1) is a rare glycogen storage disorder characterized by the abnormal accumulation of polyglucosan bodies in various tissues, particularly skeletal muscle. Caused by pathogenic variants in the RBCK1 gene, PGBM1 presents significant diagnostic challenges due to its rarity and potentially cryptic genetic mechanisms. This report describes a 12-year-old boy presenting with progressive lower limb weakness. Muscle biopsy revealed polyglucosan myopathy changes, including PAS-positive, diastase-resistant inclusions predominantly within glycogen-depleted muscle fibers. A definitive molecular diagnosis was achieved through the integration of whole-genome sequencing and RNA sequencing, which uncovered an Alu mediated homozygous intergenic inversion involving exons 1–4 of the RBCK1 gene. Based on previously reported cases of RBCK1-related PGBM1 and our patient, we observed a recurrent recombination between the RBCK1 and TRIB3 genes. This suggests that the 20p13 region is a potential structural rearrangement hotspot.