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Mutations of GEMIN5 are associated with coenzyme Q10 deficiency: long-term follow-up after treatment


GEMIN5 exerts key biological functions regulating pre-mRNAs intron removal to generate mature mRNAs. A series of patients were reported harboring mutations in GEMIN5. No treatments are currently available for this disease. We treated two of these patients with oral Coenzyme Q10 (CoQ10), which resulted in neurological improvements, although MRI abnormalities remained. Whole Exome Sequencing demonstrated compound heterozygosity at the GEMIN5 gene in both cases: Case one: p.Lys742* and p.Arg1016Cys; Case two: p.Arg1016Cys and p.Ser411Hisfs*6. Functional studies in fibroblasts revealed a decrease in CoQ10 biosynthesis compared to controls. Supplementation with exogenous CoQ10 restored it to control intracellular CoQ10 levels. Mitochondrial function was compromised, as indicated by the decrease in oxygen consumption, restored by CoQ10 supplementation. Transcriptomic analysis of GEMIN5 patients compared with controls showed general repression of genes involved in CoQ10 biosynthesis. In the rigor mortis defective flies, CoQ10 levels were decreased, and CoQ10 supplementation led to an improvement in the adult climbing assay performance, a reduction in the number of motionless flies, and partial restoration of survival. Overall, we report the association between GEMIN5 dysfunction and CoQ10 deficiency for the first time. This association opens the possibility of oral CoQ10 therapy, which is safe and has no observed side effects after long-term therapy.

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Fig. 1: Total amount and rate of CoQ10 synthesis in GEMIN5 patients’ fibroblasts.
Fig. 2: Respiratory defects in patients’ fibroblasts.
Fig. 3: COQs and MRC complexes’ protein levels in fibroblasts.
Fig. 4: Effect of CoQ10 supplementation in CoQ levels in rigor mortis adult flies.

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Data availability

Data about the basic research experiments are available upon reasonable request.

Code availability

Some of the data generated or analyzed during this study can be found within the published article and its supplementary files. Data of WES from patients is available from the corresponding author upon reasonable request.


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We are indebted to the patients and families with GEMIN5 mutations.


This research was funded by Instituto de Salud Carlos III (PI20-00340 and PI20/00541) (co-funded by European Regional Development Fund “A way to make Europe”), the Centre for Biomedical Research on Rare Diseases (CIBERER), the U.S. National Institute of Health (NIH), the National Institute of Neurological Disorders and Stroke (NINDS) R01NS134215 and Carmen de Torres grants (Institut de Recerca Sant Joan de Déu). CIBERER is an initiative from the Health Institute Carlos III.

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Authors and Affiliations



All authors critically reviewed the manuscript. RA, CSO, AGC, UP, and PN contributed to the experimental design. NJP, NR, MdMOC, PJML, CIO, JM, AN, DNdB, DSR and MP contributed to the clinical data collection, analysis, and evaluation. RU, DY, FP. performed the genetic data analysis. MVCA, ASC, DMFA, EGD, CO, AJPF, CSO, PN, RU, LS, TRF, and NJP conducting experiments, acquiring data, analyzing data, providing reagents. RA, CSO, NJP, RU, CO, MVCA drafted the manuscript and elaborated the main figures and tables.

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Correspondence to Udai Bhan Pandey, Carlos Santos-Ocaña or Rafael Artuch.

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The authors declare no competing interests.

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All patients provided the informed consent for the genetic studies and skin biopsies collection. For supplementary videos, consent from patient 1 (P1) was obtained. For patient 2 (P2), the family refused to provide informed consent to publish the video. The study was conducted following the Declaration of Helsinki, and the ethical committee of the institution of Sant Joan de Déu Hospital has approved it.

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Cascajo-Almenara, M.V., Juliá-Palacios, N., Urreizti, R. et al. Mutations of GEMIN5 are associated with coenzyme Q10 deficiency: long-term follow-up after treatment. Eur J Hum Genet 32, 426–434 (2024).

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