Novel recessive mutations in COQ4 cause severe infantile cardiomyopathy and encephalopathy associated with CoQ(10) deficiency

Coenzyme Q(10) (CoQ(10)) or ubiquinone is one of the two electron carriers in the mitochondrial respiratory chain which has an essential role in the process of oxidative phosphorylation. Defects in CoQ(10) synthesis are usually associated with the impaired function of CoQ(10)–dependent complexes I, II and III. The recessively transmitted CoQ(10) deficiency has been associated with a number of phenotypically and genetically heterogeneous groups of disorders manifesting at variable age of onset. The infantile, multisystemic presentation is usually caused by mutations in genes directly involved in CoQ(10) biosynthesis. To date, mutations in COQ1 (PDSS1 and PDSS2), COQ2, COQ4, COQ6, COQ7, COQ8A/ADCK3, COQ8B/ADCK4, and COQ9 genes have been identified in patients with primary form of CoQ(10) deficiency. Here we report novel mutations in the COQ4 gene, which were identified in an infant with profound mitochondrial disease presenting with perinatal seizures, hypertrophic cardiomyopathy and severe muscle CoQ(10) deficiency.