1. Distal myopathy due to digenic inheritance of TIA1 and SQSTM1 variants in two unrelated Spanish patients.
- Author
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Bermejo-Guerrero, Laura, de Fuenmayor Fernández-de la Hoz, Carlos Pablo, González-Quereda, Lidia, Segarra-Casas, Alba, Nedkova, Velina, Gallano, Pia, Martín-Jiménez, Paloma, Hernández-Laín, Aurelio, Olivé, Montse, Arteche-López, Ana, and Domínguez-González, Cristina
- Subjects
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HEREDITY , *MUSCLE diseases , *OLDER people , *MAGNETIC resonance imaging , *CREATINE kinase , *ARRHYTHMOGENIC right ventricular dysplasia - Abstract
• TIA - SQSTM1 digenic myopathy may be found in patients of diverse descent. • A high level of suspicion is needed to reach a diagnosis in these cases. • Description of new cases provides further evidence supporting digenic inheritance. Welander distal myopathy typically manifests in late adulthood and is caused by the founder TIA1 c.1150G> A (p.Glu384Lys) variant in families of Swedish and Finnish descent. Recently, a similar phenotype has been attributed to the digenic inheritance of TIA1 c.1070A> G (p.Asn357Ser) and SQSTM1 c.1175C>T (p.Pro392Leu) variants. We describe two unrelated Spanish patients presenting with slowly progressive gait disturbance, distal-predominant weakness, and mildly elevated creatine kinase (CK) levels since their 6th decade. Electromyography revealed abnormal spontaneous activity and a myopathic pattern. Muscle magnetic resonance imaging (MRI) showed marked fatty replacement in distal leg muscles. A muscle biopsy, performed on one patient, revealed myopathic changes with rimmed vacuoles. Both patients carried the TIA1 p.Asn357Ser and SQSTM1 p.Pro392Leu variants. Digenic inheritance is supported by evidence from unrelated pedigrees and a plausible biological interaction between both proteins in protein quality control processes. Recent functional studies and additional case descriptions further support this. Clinical suspicion is necessary to seek both variants. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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