Key result
Novel ORAI1 mutation links tubular aggregate myopathy to severe infection-triggered rhabdomyolysis.
Why the study?
The authors sought to describe the diagnostic pathway and challenges in a family with tubular aggregate myopathy caused by a rare ORAI1 variant.
Case Report (n=3)
No
The identification of a rare ORAI1 variant in a family with severe infection-triggered rhabdomyolysis broadens the phenotypic spectrum of tubular aggregate myopathy and highlights the importance of genetic testing to differentiate it from autoimmune inflammatory myopathy.
Answers are grounded in this paper and cite their sources.
May support ORAI1 testing in familial rhabdomyolysis to avoid autoimmune misclassification; extends tubular aggregate myopathy spectrum but leaves confirmation to future studies.
Introduction/Aims: Myopathies with Tubular Aggregates (TAM) are rare, chronic neuromuscular disorders that may be inherited or acquired. The aim of this report is to present the diagnostic pathway and the challenges encountered in a family with three members affected by TAM caused by a rare ORAI1 variant. Case report: Two siblings (15 and 11 years old) developed severe rhabdomyolysis triggered by a viral respiratory infection. Histopathological analysis demonstrated numerous tubular aggregates with mild focal secondary inflammatory changes and no immunophenotypic evidence of autoimmune inflammatory myopathy. Whole-exome sequencing identified a likely pathogenic heterozygous missense variant, NM_032790.3(ORAI1):c.319G>A (p.Val107Met), in the ORAI1 gene, in both children and their asymptomatic mother. Conclusions: The identification of a rare ORAI1 variant in this family supports the association with TAM, broadens the spectrum of phenotypic presentation, and illustrates the phenotypic variability that may exist even among affected members of the same family. Careful interpretation of inflammatory changes in muscle biopsy, together with immunohistochemical and genetic findings, is essential to avoid misclassification of hereditary tubular aggregate myopathy as autoimmune inflammatory myopathy.
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Ostojić et al. (2026) conducted a case report in Myopathy with Tubular Aggregates (TAM) (n=3). ORAI1 variant NM_032790.3(ORAI1):c.319G>A (p.Val107Met) was evaluated on Genetic and histopathological diagnosis. A likely pathogenic heterozygous missense variant in the ORAI1 gene (p.Val107Met) was identified in two siblings with severe infection-triggered rhabdomyolysis and their asymptomatic mother, confirming hereditary tubular aggregate myopathy.
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