{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T12:26:15Z","timestamp":1790943975193,"version":"4.1.0"},"reference-count":20,"publisher":"BMJ","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2012,1,3]]},"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                     <jats:italic>COQ4<\/jats:italic> encodes a protein that organises the multienzyme complex for the synthesis of coenzyme Q<jats:sub>10<\/jats:sub> (CoQ<jats:sub>10<\/jats:sub>). A 3.9\u2005Mb 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<jats:sub>10<\/jats:sub> deficiency.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A complete molecular and biochemical characterisation of the patient's fibroblasts and of a yeast model were performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The study found reduced <jats:italic>COQ4<\/jats:italic> expression (48% of controls), CoQ<jats:sub>10<\/jats:sub> 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<jats:sub>10<\/jats:sub> to the culture medium. Knockdown of <jats:italic>COQ4<\/jats:italic> in HeLa cells also resulted in a reduction of CoQ<jats:sub>10.<\/jats:sub> Diploid yeast haploinsufficient for <jats:italic>COQ4<\/jats:italic> displayed similar CoQ deficiency. Haploinsufficency of other genes involved in CoQ<jats:sub>10<\/jats:sub> biosynthesis does not cause CoQ deficiency, underscoring the critical role of <jats:italic>COQ4<\/jats:italic>. Oral CoQ<jats:sub>10<\/jats:sub> supplementation resulted in a significant improvement of neuromuscular symptoms, which reappeared after supplementation was temporarily discontinued.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Mutations of <jats:italic>COQ4<\/jats:italic> should be searched for in patients with CoQ<jats:sub>10<\/jats:sub> deficiency and encephalomyopathy; patients with genomic rearrangements involving <jats:italic>COQ4<\/jats:italic> should be screened for CoQ<jats:sub>10<\/jats:sub> deficiency, as they could benefit from supplementation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmedgenet-2011-100394","type":"journal-article","created":{"date-parts":[[2012,2,26]],"date-time":"2012-02-26T15:12:57Z","timestamp":1330269177000},"page":"187-191","source":"Crossref","is-referenced-by-count":101,"title":["Haploinsufficiency of <i>COQ4<\/i> causes coenzyme 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