RT Journal Article
T1 New variants expand the neurological phenotype of COQ7 deficiency
A1 Alcázar-Fabra, María
A1 Paredes-Fuentes, Abraham J.
A1 Torralba Carnerero, Manuel
A1 Moreno Fernández-Ayala, Daniel José
A1 Arroyo Luque, Antonio
A1 Sánchez Cuesta, Ana María
A1 Staiano, Carmine
A1 Sanchez-Pintos, Paula
A1 Couce, María Luz
A1 Tomás, Miguel
A1 Marco-Hernández. Ana Victoria, 
A1 Orellana, Carmen
A1 Martínez, Francisco
A1 Roselló, Mónica
A1 Caro, Alfonso
A1 Oltra Soler, Juan Silvestre
A1 Monfort, Sandra
A1 Sánchez, Alejandro
A1 Rausell, Dolores
A1 Vitoria, Isidro
A1 Toro, Mireia del
A1 García-Cazorla, Angels
A1 Natalia A. Julia-Palacios, 
A1 Jou, Cristina
A1 Yubero, Delia
A1 López, Luis Carlos
A1 Hernández Camacho, Juan Diego
A1 López-Lluch, Guillermo
A1 Ballesteros Simarro, Manuel Ángel
A1 Rodríguez Aguilera, Juan Carlos
A1 Brea Calvo, Gloria Teresa
A1 Cascajo Almenara, M.ª Victoria
A1 Artuch, Rafael
A1 Santos-Ocaña, Carlos
K1 CoQ10
K1 COQ7
K1 Mitochondrial diseases
K1 Neurological disorders
AB The protein encoded by COQ7 is required for CoQ10 synthesis in humans, hydroxylating 3-demethoxyubiquinol (DMQ10) in the second to last steps of the pathway. COQ7 mutations lead to a primary CoQ10 deficiency syndrome associated with a pleiotropic neurological disorder. This study shows the clinical, physiological, and molecular characterization of four new cases of CoQ10 primary deficiency caused by five mutations in COQ7, three of which have not yet been described, inducing mitochondrial dysfunction in all patients. However,the specific combination of the identified variants in each patient generated precise pathophysiological and molecular alterations in fibroblasts, which would explain the differential in vitro response to supplementation therapy. Our results suggest that COQ7 dysfunction could be caused by specific structural changes that affect the interaction with COQ9 required for the DMQ10 presentation to COQ7, the substrate access to the active site, and the maintenance of the active site structure. Remarkably, patients' fibroblasts share transcriptionalremodeling, supporting a modification of energy metabolism towards glycolysis, which could be an adaptive mechanism against CoQ10 deficiency. However, transcriptional analysis of mitochondria-associated pathways showed distinct and dramatic differences between patient fibroblasts, which correlated with the extent of pathophysiological and neurological alterations observed in the probands. Overall, this study suggests that the combination of precise genetic diagnostics and the availability of new structural models of human proteins could help explain the origin of phenotypic pleiotropy observed in some genetic diseases and the different responses to available therapies.
PB Wiley
YR 2024
FD 2024-04-24
LK https://hdl.handle.net/10433/23255
UL https://hdl.handle.net/10433/23255
LA en
NO Fabra MA, Paredes-Fuentes AJ, Torralba Carnerero M, et al. New variants expand the neurological phenotype of COQ7 deficiency. J Inherit Metab Dis. 2024;1‐22. doi:10.1002/jimd.12776
NO Centro Andaluz de Biología del Desarrollo
NO Departamento de Fisiología, Anatomía y Biología Celular
NO CIBER de Enfermedades Raras
DS RIO
RD May 14, 2026