دورية أكاديمية
Expanding the phenotypic spectrum ofTRAPPC11-related muscular dystrophy: 25 Roma individuals carrying a founder variant
| العنوان: | Expanding the phenotypic spectrum ofTRAPPC11-related muscular dystrophy: 25 Roma individuals carrying a founder variant |
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| المؤلفون: | Justel, Maria, Jou, Cristina, Sariego-Jamardo, Andrea, Juliá-Palacios, Natalia Alexandra, Ortez, Carlos, Poch, Maria Luisa, Hedrera-Fernandez, Antonio, Gomez-Martin, Hilario, Codina, Anna, Dominguez-Carral, Jana, Muxart, Jordi, Hernández-Laín, Aurelio, Vila-Bedmar, Sara, Zulaica, Miren, Castro, Margarita del Carmen, de la Osa-Langreo, Alberto, Peña-Valenceja, Alfonso, Marcos-Vadillo, Elena, Prieto-Matos, Pablo, Pascual-Pascual, Samuel Ignacio, López de Munain, Adolfo, Camacho, Ana, Estevez-Arias, Berta, Musokhranova, Uliana, Olivella, Mireia, Oyarzábal, Alfonso, Jimenez-Mallebrera, Cecilia, Domínguez-González, Cristina, Nascimento, Andrés, García-Cazorla, Àngels, Natera-de Benito, Daniel, Cancho-Candela, Ramon |
| بيانات النشر: | BMJ |
| سنة النشر: | 2023 |
| المجموعة: | UVaDOC - Repositorio Documental de la Universidad de Valladolid |
| الوصف: | Background Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of genetically determined muscle disorders. TRAPPC11-related LGMD is an autosomal-recessive condition characterised by muscle weakness and intellectual disability. Methods A clinical and histopathological characterisation of 25 Roma individuals with LGMD R18 caused by the homozygous TRAPPC11 c.1287+5G>A variant is reported. Functional effects of the variant on mitochondrial function were investigated. Results The c.1287+5G>A variant leads to a phenotype characterised by early onset muscle weakness, movement disorder, intellectual disability and elevated serum creatine kinase, which is similar to other series. As novel clinical findings, we found that microcephaly is almost universal and that infections in the first years of life seem to act as triggers for a psychomotor regression and onset of seizures in several individuals with TRAPPC11 variants, who showed pseudometabolic crises triggered by infections. Our functional studies expanded the role of TRAPPC11 deficiency in mitochondrial function, as a decreased mitochondrial ATP production capacity and alterations in the mitochondrial network architecture were detected. Conclusion We provide a comprehensive phenotypic characterisation of the pathogenic variant TRAPPC11 c.1287+5G>A, which is founder in the Roma population. Our observations indicate that some typical features of golgipathies, such as microcephaly and clinical decompensation associated with infections, are prevalent in individuals with LGMD R18 |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | Spanish; Castilian |
| تدمد: | 0022-2593 1468-6244 |
| العلاقة: | https://doi.org/10.1136/jmg-2022-109132Test; Journal of Medical Genetics. 2023 May 16:jmg-2022-109132.; https://uvadoc.uva.es/handle/10324/64655Test; 965; 10; 973; Journal of Medical Genetics; 60 |
| DOI: | 10.1136/jmg-2022-109132 |
| الإتاحة: | https://doi.org/10.1136/jmg-2022-109132Test https://uvadoc.uva.es/handle/10324/64655Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.870190C1 |
| قاعدة البيانات: | BASE |
| تدمد: | 00222593 14686244 |
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| DOI: | 10.1136/jmg-2022-109132 |