C1QBP – Combined Oxidative Phosphorylation Deficiency 33

C1QBP encodes the mitochondrial matrix protein p32, which is essential for mitochondrial protein translation and maintenance of oxidative phosphorylation (OXPHOS). A 2020 study described two male siblings born to consanguineous Chinese parents presenting in infancy with exercise intolerance, ptosis, myocardial hypertrophy and elevated blood lactate. Both brothers were homozygous for NM_001212.4:c.823C>T (p.Leu275Phe) and their heterozygous parents were asymptomatic, consistent with autosomal recessive inheritance (PMID:33344382).

Functional evidence supports a loss‐of‐function mechanism: C1QBP‐deficient models and patient‐derived cells exhibit impaired mitochondrial translation, reduced OXPHOS activity and cardiomyopathic features mirroring human disease (PMID:35310974). Truncating and missense C1QBP mutations cluster in conserved coiled‐coil domains, resulting in defective trimerization and diminished mitochondrial import. Rescue experiments in cellular models restore mitochondrial function, underscoring the causal role of biallelic C1QBP variants.

Key Take-home: Biallelic C1QBP mutations cause early-onset COXPD 33 via a loss-of-function mechanism; genetic testing informs diagnosis and guides management.

References

• Frontiers in pediatrics • 2020 • Early Onset of Combined Oxidative Phosphorylation Deficiency in Two Chinese Brothers Caused by a Homozygous (Leu275Phe) Mutation in the C1QBP Gene. PMID:33344382
• Frontiers in cardiovascular medicine • 2022 • Complement C1q Binding Protein (C1QBP): Physiological Functions, Mutation-Associated Mitochondrial Cardiomyopathy and Current Disease Models. PMID:35310974

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