RT Journal Article
T1 Identification of a new COQ4 spliceogenic variant causing severe primary coenzyme Q deficiency
A1 Alcázar-Fabra, María
A1 Østergaard, Elsebet
A1 Moreno Fernández-Ayala, Daniel José
A1 Desbats, Maria Andrea
A1 Morbidoni, Valeria
A1 Tomás-Gallardo, Laura
A1 García Corzo, Laura
A1 Blanquer Rosselló, Maria del Mar
A1 Bartlett, Abigail K
A1 Sánchez Cuesta, Ana María
A1 Sena, Lucía
A1 Cortés-Rodríguez, Ana María
A1 Cascajo Almenara, M.ª Victoria
A1 Pagliarini, David
A1 Trevison, Eva
A1 Gronborg, Sabine
A1 Brea Calvo, Gloria Teresa
K1 COQ4
K1 Coenzyme Q10 deficiency
K1 Spliceogenic variant
K1 Mitochondrial disorder
K1 Hybrid minigene
K1 WES
AB Background and aims: Primary Coenzyme Q (CoQ) deficiency caused by COQ4 defects is a clinically heterogeneous mitochondrial condition characterized by reduced levels of CoQ10 in tissues. Next-generation sequencing has lately boosted the genetic diagnosis of an increasing number of patients. Still, functional validation of new variants of uncertain significance is essential for an adequate diagnosis, proper clinical management, treatment, and genetic counseling.Materials and methods: Both fibroblasts from a proband with COQ4 deficiency and a COQ4 knockout cell model have been characterized by a combination of biochemical and genetic analysis (HPLC lipid analysis, Oxygen consumption, minigene analysis, RNAseq, among others).Results: Here, we report the case of a subject harboring a new variant of the COQ4 gene in compound heterozygosis, which shows severe clinical manifestations. We present the molecular characterization of this new pathogenic variant affecting the splicing of COQ4.Conclusion: Our results highlight the importance of expanding the genetic analysis beyond the coding sequence to reduce the misdiagnosis of primary CoQ deficiency patients.
PB Elsevier
YR 2025
FD 2025
LK https://hdl.handle.net/10433/22350
UL https://hdl.handle.net/10433/22350
LA en
NO María Alcázar-Fabra, Elsebet Østergaard, Daniel J.M. Fernández-Ayala, María Andrea Desbats, Valeria Morbidoni, Laura Tomás-Gallado, Laura García-Corzo, María del Mar Blanquer-Roselló, Abigail K. Bartlett, Ana Sánchez-Cuesta, Lucía Sena, Ana Cortés-Rodríguez, María Victoria Cascajo-Almenara, David J. Pagliarini, Eva Trevisson, Sabine W. Gronborg, Gloria Brea-Calvo, Identification of a new COQ4 spliceogenic variant causing severe primary coenzyme Q deficiency, Molecular Genetics and Metabolism Reports, Volume 42, 2025,
NO P18-RT- 4572UPO-1265673
NO Universidad Pablo de Olavide-CABD
DS RIO
RD Apr 24, 2026