Clinical spectrum in multiple families with primary COQ10 deficiency.

Coenzyme Q10/ COQ10 , an essential cofactor in the electron-transport chain is involved in ATP production. Primary COQ10 deficiency is clinically and genetically a heterogeneous group of mitochondrial disorders caused by defects in the COQ10 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 COQ10 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 Q10 deficiency from other similar conditions. Given that some features of primary coenzyme Q10 deficiency may improve with exogenous COQ10 , early diagnosis is very important.

Automatic classification of gait patterns in children with cerebral palsy using fuzzy clustering method.

BACKGROUND: Subjective classification of gait pattern in children with cerebral palsy depends on the assessor's experience, while mathematical methods produce virtual groups with no clinical interpretation. METHODS: In a retrospective study, gait data from 66 children (132 limbs) with a mean age of 9.6 (SD 3.7) years with cerebral palsy and no history of surgery or botulinum toxin injection were reviewed. The gait pattern of each limb was classified in four groups according to Rodda using three methods: 1) a team of experts subjectively assigning a gait pattern, 2) using the plantarflexor-knee extension couple index introduced by Sangeux et al., and 3) employing a fuzzy algorithm to translate the experiences of experts into objective rules and execute a clustering tool. To define fuzzy repeated-measures, 75% of the members in each group were used, and the remaining were used for validation. Eight parameters were objectively extracted from kinematic data for each group and compared using repeated measure ANOVA and post-hoc analysis was performed. Finally, the results of the clustering of the latter two methods were compared to the subjective method. FINDINGS: The plantarflexor-knee extension couple index achieved 86% accuracy while the fuzzy system yielded a 98% accuracy. The most substantial errors occurred between jump and apparent in both methods. INTERPRETATION: The presented method is a fast, reliable, and objective fuzzy clustering system to classify gait patterns in cerebral palsy, which produces clinically-relevant results. It can provide a universal common language for researchers.