COQ3 – Multiple Sclerosis

The association between COQ3 and multiple sclerosis (MONDO_0005301) is supported by limited genetic evidence. Two pediatric probands with relapsing‑remitting multiple sclerosis were identified through whole exome sequencing and found to harbor rare variants in COQ3, including the variant c.250G>A (p.Gly84Ser) (PMID:30963028). Although these findings implicate COQ3 in an iron‑responsive subtype of multiple sclerosis, no additional segregation data from affected relatives have been reported, and recurrence of this variant has not been firmly established. Inheritance is presumed to follow an autosomal recessive pattern based on the screening framework used in the study. This initial genetic observation provides a preliminary link that requires further replication with larger cohorts and additional familial studies.

Complementary functional evidence further supports a role for COQ3 in disease pathogenesis. Experimental studies have demonstrated that COQ3 is essential for coenzyme Q biosynthesis and mitochondrial electron transport, with perturbations in its activity potentially contributing to impaired myelination seen in multiple sclerosis (PMID:36552517; PMID:32194061). Biochemical assays and protein complex analyses in model systems revealed that disruption of COQ3 function can lead to decreased CoQ10 levels and consequent mitochondrial dysfunction. These mechanistic insights provide biological plausibility for the clinical findings while underscoring the need for further experimental validation and in vivo modeling. In summary, current evidence presents a limited yet promising association between COQ3 and multiple sclerosis that could refine diagnostic decisions and inform future therapeutic strategies.

References

• Molecular genetics and metabolism reports • 2019 • Identification of an iron-responsive subtype in two children diagnosed with relapsing‑remitting multiple sclerosis using whole exome sequencing PMID:30963028
• Antioxidants (Basel, Switzerland) • 2022 • Predicting and Understanding the Pathology of Single Nucleotide Variants in Human COQ Genes PMID:36552517
• Biochimica et biophysica acta. Bioenergetics • 2020 • Characterization of human mitochondrial PDSS and COQ proteins and their roles in maintaining coenzyme Q10 levels and each other’s stability PMID:32194061

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