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To date, mutations in nine proteins required for the biosynthesis of CoQ<jats:sub>10<\/jats:sub> cause CoQ<jats:sub>10<\/jats:sub> deficiency with varying clinical presentations. In 2009 the first patient with mutations in COQ9 was reported in an infant with a neonatal\u2010onset, primary CoQ<jats:sub>10<\/jats:sub> deficiency with multi\u2010system disease. Here we describe four siblings with a previously undiagnosed lethal disorder characterized by oligohydramnios and intrauterine growth restriction, variable cardiomyopathy, anemia, and renal anomalies. The first and third pregnancy resulted in live born babies with abnormal tone who developed severe, treatment unresponsive lactic acidosis after birth and died hours later. Autopsy on one of the siblings demonstrated brain changes suggestive of the subacute necrotizing encephalopathy of Leigh disease. Whole\u2010exome sequencing (WES) revealed the siblings shared compound heterozygous mutations in the <jats:italic>COQ9<\/jats:italic> gene with both variants predicted to affect splicing. RT\u2010PCR on RNA from patient fibroblasts revealed that the c.521\u2009+\u20092 T\u2009&gt;\u2009C variant resulted in splicing out of exons 4\u20135 and the c.711\u2009+\u20093G\u2009&gt;\u2009C variant spliced out exon 6, resulting in undetectable levels of COQ9 protein in patient fibroblasts. The biochemical profile of patient fibroblasts demonstrated a drastic reduction in CoQ<jats:sub>10<\/jats:sub> levels. An additional peak on the chromatogram may represent accumulation of demethoxy coenzyme Q (DMQ), which was shown previously to accumulate as a result of a defect in COQ9. This family expands our understanding of this rare metabolic disease and highlights the prenatal onset, clinical variability, severity, and biochemical profile associated with COQ9\u2010related CoQ<jats:sub>10<\/jats:sub> deficiencies.<\/jats:p>","DOI":"10.1007\/s10545-017-0122-7","type":"journal-article","created":{"date-parts":[[2018,3,20]],"date-time":"2018-03-20T14:53:36Z","timestamp":1521557616000},"page":"719-729","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["A family segregating lethal neonatal coenzyme Q<sub>10<\/sub> deficiency caused by mutations in COQ9"],"prefix":"10.1002","volume":"41","author":[{"given":"Amanda C.","family":"Smith","sequence":"first","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa Ottawa ON Canada"},{"name":"Department of Genetics Children's Hospital of Eastern Ontario Ottawa ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Ito","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa Ottawa ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Afsana","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa Ottawa ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy A.","family":"Schwartzentruber","sequence":"additional","affiliation":[{"name":"McGill University and Genome Quebec Innovation Centre Montr\u00e9al QC Canada"},{"name":"Department of Human Genetics McGill University Montr\u00e9al QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandree L.","family":"Beaulieu","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa Ottawa ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Aberg","sequence":"additional","affiliation":[{"name":"Maritime Medical Genetics Service IWK Health Centre P.O. Box 9700 5850 University Avenue Halifax NS B3K 6R8 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacek","family":"Majewski","sequence":"additional","affiliation":[{"name":"McGill University and Genome Quebec Innovation Centre Montr\u00e9al QC Canada"},{"name":"Department of Human Genetics McGill University Montr\u00e9al QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis E.","family":"Bulman","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa Ottawa ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karina","family":"Horsting\u2010Wethly","sequence":"additional","affiliation":[{"name":"Radboud Center for Mitochondrial Medicine, Translational Metabolic Laboratory Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana Vermunt\u2010de","family":"Koning","sequence":"additional","affiliation":[{"name":"Radboud Center for Mitochondrial Medicine, Translational Metabolic Laboratory Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Care4Rare Canada Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Rodenburg","sequence":"additional","affiliation":[{"name":"Radboud Center for Mitochondrial Medicine, Translational Metabolic Laboratory Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kym M.","family":"Boycott","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa Ottawa ON Canada"},{"name":"Department of Genetics Children's Hospital of Eastern Ontario Ottawa ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynette S.","family":"Penney","sequence":"additional","affiliation":[{"name":"Maritime Medical Genetics Service IWK Health Centre P.O. 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