RT info:eu-repo/semantics/article
T1 Expanding the phenotypic spectrum ofTRAPPC11-related muscular dystrophy: 25 Roma individuals carrying a founder variant
A1 Justel, Maria
A1 Jou, Cristina
A1 Sariego-Jamardo, Andrea
A1 Juliá-Palacios, Natalia Alexandra
A1 Ortez, Carlos
A1 Poch, Maria Luisa
A1 Hedrera Fernández, Antonio
A1 Gomez-Martin, Hilario
A1 Codina, Anna
A1 Dominguez-Carral, Jana
A1 Muxart, Jordi
A1 Hernández-Laín, Aurelio
A1 Vila-Bedmar, Sara
A1 Zulaica, Miren
A1 Castro, Margarita del Carmen
A1 de la Osa-Langreo, Alberto
A1 Peña-Valenceja, Alfonso
A1 Marcos-Vadillo, Elena
A1 Prieto-Matos, Pablo
A1 Pascual-Pascual, Samuel Ignacio
A1 López de Munain, Adolfo
A1 Camacho, Ana
A1 Estevez-Arias, Berta
A1 Musokhranova, Uliana
A1 Olivella, Mireia
A1 Oyarzábal, Alfonso
A1 Jimenez-Mallebrera, Cecilia
A1 Domínguez-González, Cristina
A1 Nascimento, Andrés
A1 García Cazorla, Àngels
A1 Natera-de Benito, Daniel
A1 Cancho Candela, Ramón
AB 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
PB BMJ
SN 0022-2593
YR 2023
FD 2023
LK https://uvadoc.uva.es/handle/10324/64655
UL https://uvadoc.uva.es/handle/10324/64655
LA spa
NO Journal of Medical Genetics. 2023 May 16:jmg-2022-109132.
DS UVaDOC
RD 24-abr-2025