Mutations outside the N-terminal part of <italic>RBCK1</italic> may cause polyglucosan body myopathy with immunological dysfunction: expanding the genotype–phenotype spectrum.

A subset of patients with polyglucosan body myopathy was found to have underlying mutations in the <italic>RBCK1</italic> gene. Affected patients may display diverse symptoms ranging from skeletal muscular weakness, cardiomyopathy to chronic autoinflammation and immunodeficiency. It was suggested that the exact localization of the mutation within the gene might be responsible for the specific phenotype, with N-terminal mutations causing severe immunological dysfunction and mutations in the middle or C-terminal part leading to a myopathy phenotype. We report the clinical, immunological and genetic findings of two unrelated individuals suffering from a childhood-onset <italic>RBCK1</italic>-asscociated disease caused by the same homozygous truncating mutation (NM_031229.2:c.896_899del, p.Glu299Valfs*46) in the middle part of the <italic>RBCK1</italic> gene. Our patients suffered from a myopathy with cardiac involvement, but in contrast to previous reports on mutations in this part of the gene, also displayed signs of autoinflammation and immunodeficiency. Our report suggests that <italic>RBCK1</italic> mutations at locations that were previously thought to lack immunological features may also present with immunological dysfunction later in the disease course. This notably broadens the genotype–phenotype correlation of <italic>RBCK1</italic>-related polyglucosan body myopathy. [ABSTRACT FROM AUTHOR]