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Purpose: Missense variants clustering in the BTB domain region of RHOBTB2 cause a developmental and epileptic encephalopathy with early-onset seizures and severe intellectual disability., Methods: By international collaboration, we assembled individuals with pathogenic RHOBTB2 variants and a variable spectrum of neurodevelopmental disorders. By western blotting, we investigated the consequences of missense variants in vitro., Results: In accordance with previous observations, de novo heterozygous missense variants in the BTB domain region led to a severe developmental and epileptic encephalopathy in 16 individuals. Now, we also identified de novo missense variants in the GTPase domain in 6 individuals with apparently more variable neurodevelopmental phenotypes with or without epilepsy. In contrast to variants in the BTB domain region, variants in the GTPase domain do not impair proteasomal degradation of RHOBTB2 in vitro, indicating different functional consequences. Furthermore, we observed biallelic splice-site and truncating variants in 9 families with variable neurodevelopmental phenotypes, indicating that complete loss of RHOBTB2 is pathogenic as well., Conclusion: By identifying genotype-phenotype correlations regarding location and consequences of de novo missense variants in RHOBTB2 and by identifying biallelic truncating variants, we further delineate and expand the molecular and clinical spectrum of RHOBTB2-related phenotypes, including both autosomal dominant and recessive neurodevelopmental disorders., Competing Interests: Conflict of Interest Jeffrey B. Ratliff serves on the editorial board for the journal Neurology and has received consulting fees from Supernus Pharmaceuticals. All other authors declare no conflicts of interest., (Copyright © 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

The United States (U.S.) resident Marshallese population is growing rapidly. Subsequent to this growth, Marshallese patients experience language and cultural barriers when attempting to access medical care in the U.S. This study: (a) documents how the Marshallese refer to biological and adopted family members; (b) identifies barriers encountered by Marshallese when seeking medical care; and (c) describes effective communication strategies for healthcare providers to use when treating Marshallese patients. Six key informant interviews were conducted in English with bicultural (U.S. and native Marshallese) informants, the majority of whom were women who worked in a healthcare setting. Participants were recruited through the Center for Pacific Islander Health in Arkansas and through personal contacts within the Marshallese community. Based on the study findings, examples of how providers can make genetic services more accessible and meaningful for Marshallese patients are also provided. This study is particularly relevant to genetic counselors as the number of Marshallese patients and families needing their services is growing., (© The Authors. Journal of Genetic Counseling published by Wiley Periodicals LLC on behalf of National Society of Genetic Counselors.)

The degree to which "brain training" can improve general cognition, resulting in improved performance on tasks dissimilar from the trained tasks (transfer of training), is a controversial topic. Here, we tested the degree to which cognitive training, in the form of gamified training activities that have demonstrated some degree of success in the past, might result in broad transfer. Sixty older adults were randomly assigned to a gamified cognitive training intervention or to an active control condition that involved playing word and number puzzle games. Participants were provided with tablet computers and asked to engage in their assigned training for 30 45-min training sessions over the course of 1 month. Although intervention adherence was acceptable, little evidence for transfer was observed except for the performance of one task that most resembled the gamified cognitive training: There was a trend for greater improvement on a version of the corsi block tapping task for the cognitive training group relative to the control group. This task was very similar to one of the training games. Results suggest that participants were learning specific skills and strategies from game training that influenced their performance on a similar task. However, even this near-transfer effect was weak. Although the results were not positive with respect to broad transfer of training, longer duration studies with larger samples and the addition of a retention period are necessary before the benefit of this specific intervention can be ruled out.