Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals.

Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants in the two genes that encode histone H3.3 (H3-3A/H3F3A and H3-3B/H3F3B) [1-4]. This syndrome is characterized by developmental delay/intellectual disability, craniofacial anomalies, hyper/hypotonia, and abnormal neuroimaging [1, 5]. BLBS was initially categorized as a progressive neurodegenerative syndrome caused by de novo heterozygous variants in either H3-3A or H3-3B [1-4]. Here, we analyze the data of the 58 previously published individuals along 38 unpublished, unrelated individuals. In this larger cohort of 96 people, we identify causative missense, synonymous, and stop-loss variants. We also expand upon the phenotypic characterization by elaborating on the neurodevelopmental component of BLBS. Notably, phenotypic heterogeneity was present even amongst individuals harboring the same variant. To explore the complex phenotypic variation in this expanded cohort, the relationships between syndromic phenotypes with three variables of interest were interrogated: sex, gene containing the causative variant, and variant location in the H3.3 protein. While specific genotype-phenotype correlations have not been conclusively delineated, the results presented here suggest that the location of the variants within the H3.3 protein and the affected gene (H3-3A or H3-3B) contribute more to the severity of distinct phenotypes than sex. Since these variables do not account for all BLBS phenotypic variability, these findings suggest that additional factors may play a role in modifying the phenotypes of affected individuals. Histones are poised at the interface of genetics and epigenetics, highlighting the potential role for gene-environment interactions and the importance of future research.

TBCK syndrome: a rare multi-organ neurodegenerative disease.

TBCK syndrome is an autosomal recessive disorder primarily characterized by global developmental delay, hypotonia, abnormal magnetic resonance imaging (MRI), and distinctive craniofacial phenotypes. High variability is observed among affected individuals and their corresponding variants, making clinical diagnosis challenging. Here, we discuss recent breakthroughs in clinical considerations, TBCK function, and therapeutic development.

Drought alters the trophic role of an opportunistic generalist in an aquatic ecosystem.

Abiotic change can alter species interactions by modifying species' trophic roles, but this has not been well studied. Until now, bromeliad-dwelling tipulid larvae were thought to positively affect other macroinvertebrates via a facilitative processing chain. However, under drought, we found the opposite. We performed two microcosm experiments in which we factorially manipulated water level and predation by tipulids, and measured the effects on mosquito and chironomid larvae. The experiments differed in whether high water was contrasted with low or no water, allowing us to distinguish between the effects of desiccation stress (no water) and increased encounter rates due to compression of habitat or reductions in prey mobility (low and no water). We also included a caged tipulid treatment to measure any non-consumptive effects. As well as directly reducing prey survival, reductions in water level indirectly decreased chironomid and mosquito survival by altering the trophic role of tipulids. Our results suggest that increased encounter rates with prey led to tipulids becoming predatory under simulated drought, as tipulids consumed prey under both low and no water. When water level was high, tipulids exerted negative non-consumptive effects on prey survival. Because opportunistic predators are common throughout aquatic ecosystems, the effects of drought on the trophic roles of species may be widespread. Such restructuring of food webs should be considered when attempting to predict the ecological effects of environmental change.