Coenzyme Q 10/ COQ 10 , an essential cofactor in the electron-transport chain is involved in ATP production. Primary COQ 10 deficiency is clinically and genetically a heterogeneous group of mitochondrial disorders caused by defects in the COQ 10 synthesis pathway. Its mode of inheritance is autosomal recessive and it is characterized by metabolic abnormalities and multisystem involvement including neurological features. Mutations in 10 genes have been identified concerning this group of diseases, so far. Among those, variants of the COQ7 gene are very rare and confined to three patients with Asian ancestry. Here, we present the clinical features and results of whole-exome sequencing (WES) of three Iranian unrelated families affected by primary COQ 10 deficiency. Three homozygous variants in COQ2, COQ4, and COQ7 genes were identified. Candidate variants of the COQ2 and COQ4 genes were novel and associated with the cerebellar signs and multisystem involvement, whereas, the known variant in COQ7 was associated with a mild phenotype that was initially diagnosed as hereditary spastic paraplegia (HSP). This variant has already been reported in a Canadian girl with similar presentations that also originated from Iran suggesting both patients may share a common ancestor. Due to extensive heterogeneity in this group of disorders, and overlap with other mitochondrial/neurological disorders, WES may be helpful to distinguish primary coenzyme Q 10 deficiency from other similar conditions. Given that some features of primary coenzyme Q 10 deficiency may improve with exogenous COQ 10 , early diagnosis is very important.COQ2, COQ4 and COQ7 genes, hereditary spastic paraplegia (HSP), mitochondrial disease, primary COQ 10 deficiencies, whole-exome sequencing (WES) | INTRODUCTIONCoenzyme Q 10 (COQ 10 ), also named ubiquinone, is an electron carrier that contributes as a major electron transporter in the mitochondrial respiratory chain for energy production. COQ 10 structure comprises a long hydrophobic polyisoprenoid tail and a benzoquinone ring for redox activities allowing it to act as a cofactor for many enzymes and uncoupling proteins. The polyisoprenoid tail is synthesized by COQ1 corresponding protein and its length varies in different species. In humans, it consists of 10 isoprene units (COQ 10
BackgroundSPG11 mutations can cause autosomal recessive hereditary spastic paraplegia (ARHSP) and juvenile amyotrophic lateral sclerosis (JALS). Because these diseases share some clinical presentations and both can be caused by SPG11 mutations, it was considered that definitive diagnosis may not be straight forward.MethodsThe DNAs of referred ARHSP and JALS patients were exome sequenced. Clinical data of patients with SPG11 mutations were gathered by interviews and neurological examinations including electrodiagnosis (EDX) and magnetic resonance imaging (MRI).ResultsEight probands with SPG11 mutations were identified. Two mutations are novel. Among seven Iranian probands, six carried the p.Glu1026Argfs*4‐causing mutation. All eight patients had features known to be present in both ARHSP and JALS. Additionally and surprisingly, presence of both thin corpus callosum (TCC) on MRI and motor neuronopathy were also observed in seven patients. These presentations are, respectively, key suggestive features of ARHSP and JALS.ConclusionWe suggest that rather than ARHSP or JALS, combined ARHSP/JALS is the appropriate description of seven patients studied. Criteria for ARHSP, JALS, and combined ARHSP/JALS designations among patients with SPG11 mutations are suggested. The importance of performing both EDX and MRI is emphasized. Initial screening for p.Glu1026Argfs*4 may facilitate SPG11 screenings in Iranian patients.
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