New variants expand the neurological phenotype of COQ7 deficiency.

The protein encoded by COQ7 is required for CoQ10 synthesis in humans, hydroxylating 3-demethoxyubiquinol (DMQ10) in the second to last steps of the pathway. COQ7 mutations lead to a primary CoQ10 deficiency syndrome associated with a pleiotropic neurological disorder. This study shows the clinical, physiological, and molecular characterization of four new cases of CoQ10 primary deficiency caused by five mutations in COQ7, three of which have not yet been described, inducing mitochondrial dysfunction in all patients. However, the specific combination of the identified variants in each patient generated precise pathophysiological and molecular alterations in fibroblasts, which would explain the differential in vitro response to supplementation therapy. Our results suggest that COQ7 dysfunction could be caused by specific structural changes that affect the interaction with COQ9 required for the DMQ10 presentation to COQ7, the substrate access to the active site, and the maintenance of the active site structure. Remarkably, patients' fibroblasts share transcriptional remodeling, supporting a modification of energy metabolism towards glycolysis, which could be an adaptive mechanism against CoQ10 deficiency. However, transcriptional analysis of mitochondria-associated pathways showed distinct and dramatic differences between patient fibroblasts, which correlated with the extent of pathophysiological and neurological alterations observed in the probands. Overall, this study suggests that the combination of precise genetic diagnostics and the availability of new structural models of human proteins could help explain the origin of phenotypic pleiotropy observed in some genetic diseases and the different responses to available therapies.

Cross-Language Associations in the Development of Preschoolers' Receptive and Expressive Vocabulary.

The increasing population of dual language learners (DLLs) entering preschool classrooms highlights a continued need for research on the development of dual language acquisition, and specifically vocabulary skills, in this age group. This study describes young DLL children's (N = 177) vocabulary development in both English and Spanish simultaneously, and how vocabulary skills in each language relate to one another, during a contextual shift that places greater emphasis on the acquisition of academic English language skills. Findings demonstrated that DLL preschoolers made gains in vocabulary in both languages with more change evidenced in receptive, in comparison to expressive, vocabulary as well as in English in comparison to Spanish. When examining whether children's vocabulary scores in one language at the beginning of preschool interact with their vocabulary scores in the other language to predict vocabulary growth, no significant associations were found for receptive vocabulary. In contrast, the interaction between initial English and Spanish expressive vocabulary scores was negatively related to growth in English expressive vocabulary. This cross-language association suggests that children who have low expressive vocabulary skills in both languages tend to grow faster in their English expressive vocabulary. The study extends previous work on dual language development by examining growth in expressive and receptive vocabulary in both English and Spanish. It also provides suggestions for future work to inform a more comprehensive understanding of DLL children's development in both languages.