Key result
Five pathogenic RYR1 variants in Dusty Core Disease show severe recessive and moderate dominant inheritance.
Why the study?
Dusty Core Disease was previously associated only with biallelic recessive RYR1 mutations, prompting analysis of clinical, pathological, and mutational features in affected patients.
Case Report (n=4)
Yes
This study expands the genetic and clinical landscape of Dusty Core Disease by identifying novel RYR1 variants and demonstrating that the disease can present with an autosomal dominant, adult-onset inheritance pattern.
Answers are grounded in this paper and cite their sources.
Clinicians should consider dominant RYR1 variants in adult myopathy; extends known spectrum of Dusty Core Disease to moderate inheritance.
Core myopathies are congenital diseases with clinical, pathological and genetic heterogeneity. Main histological features are fiber "cores" showing a focally reduced oxidative enzyme activity. Dusty Core Disease (DuCD) differs from Central Core Myopathy for the presence of irregular areas, without clear borders and round/ovoidal shape, and myofibrillar disorganization characterized by reddish purple granular material depositions. This disorder is defined clinically by severe phenotypes with early onset of disease and molecularly by low level of RyR1 in muscle. Until now DuCD was associated only to biallelic recessive RYR1 mutations. We analyzed the clinical aspects, pathological features and mutational spectrum of four DuCD patients, belonging to our cohort of Congenital Myopathy probands. Molecular analysis detected 5 different RYR1 pathogenic variants, two of them so far unreported. Patients presented a heterogeneous phenotype ranging from severe recessive infantile forms to moderate dominant adult-onset presentations. Histological, immunological and ultrastructural techniques were employed to validate these dominant cases, which expand our knowledge on the inheritance of this subgroup of diseases.
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Zanotti et al. (2026) conducted a case report in Dusty Core Disease (n=4). Genetic and histopathological analysis of four patients with Dusty Core Disease identified five RYR1 pathogenic variants, revealing both severe recessive and moderate dominant inheritance patterns.
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