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Background: COQ4 encodes a protein that organises the multienzyme complex for the synthesis of coenzyme Q(10) (CoQ(10)). A 3.9 Mb deletion of chromosome 9q34.13 was identified in a 3-year-old boy with mental retardation, encephalomyopathy and dysmorphic features. Because the deletion encompassed COQ4, the patient was screened for CoQ(10) deficiency., Methods: A complete molecular and biochemical characterisation of the patient's fibroblasts and of a yeast model were performed., Results: The study found reduced COQ4 expression (48% of controls), CoQ(10) content and biosynthetic rate (44% and 43% of controls), and activities of respiratory chain complex II+III. Cells displayed a growth defect that was corrected by the addition of CoQ(10) to the culture medium. Knockdown of COQ4 in HeLa cells also resulted in a reduction of CoQ(10.) Diploid yeast haploinsufficient for COQ4 displayed similar CoQ deficiency. Haploinsufficency of other genes involved in CoQ(10) biosynthesis does not cause CoQ deficiency, underscoring the critical role of COQ4. Oral CoQ(10) supplementation resulted in a significant improvement of neuromuscular symptoms, which reappeared after supplementation was temporarily discontinued., Conclusion: Mutations of COQ4 should be searched for in patients with CoQ(10) deficiency and encephalomyopathy; patients with genomic rearrangements involving COQ4 should be screened for CoQ(10) deficiency, as they could benefit from supplementation.

Facioscapulohumeral dystrophy (FSHD), one of the most common forms of muscular dystrophy, derives its name from the patients' selective, often asymmetric clinical distribution of muscle weakness. Interestingly, affected and non affected areas can coexist in the same patient for many years. The molecular hallmark is total deletion of the subtelomeric D4Z4 repeat on chromosome 4q. There is no specific treatment. Gene therapy is unlikely to be feasible, as no alterations have been found in the genes located in this subtelomeric region. Muscular dystrophies are characterized by the coexistence of genetically induced muscle degeneration and compensatory muscle regeneration by myoblast proliferation from satellite cells; muscle weakness and atrophy appears when this mechanism is overwhelmed. Cell therapy with autologous myoblasts would, in theory, be a simple way of boosting the regenerative process and of preventing or delaying muscle degeneration. This approach might also avoid the use of toxic immunotherapies. By using a recent very-high-yield cell culture method, we analyzed the proliferation and differentiation of myoblasts obtained from FSHD patients, both ex vivo and in vivo (by intramuscular injection to immunodeficient mice). Myoblasts were obtained by muscle biopsy from five FSHD patients harboring the D4Z4 deletion. We selected the vastus lateralis muscle, which exhibited no clinical, radiological or pathological signs of dystrophy. The growth characteristics of these cells were compared with those of cells from normal control muscles, based on the culture yield, phenotypic characterization with anti-CD56 and anti-desmin antibodies, and the capacity for differentiation (myotube production in vitro and human dystrophin expression one month after injection to Rag2 immunodeficient mice). Patients' cells recovered from 1 g of muscle biopsy specimen resembled control cells in terms of their growth kinetics, culture yield, and capacity to differentiate and produce mature muscle cells. These results indicate that myoblasts taken from unaffected muscle of patients with FSHD warrant testing in a human cell therapy trial.