Before pregnancy, genetic carrier screening can identify couples who both carry changes linked to the same inherited disorder, allowing them to estimate the chance of having an affected child. Traditionally, testing was chosen based on a person’s reported ethnic background, on the belief that certain variants occur primarily in specific populations. In this study, we […]
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BHLHE22 monoallelic and biallelic variants cause a neurodevelopmental disorder with agenesis of the corpus callosum, intellectual disability, abnormal muscle tone and movement abnormalities (Contributed by Dr. Emanuela Argilli)
This study identifies a previously unrecognized genetic disorder caused by changes in the BHLHE22 gene. Clinical and genetic information from 15 affected individuals in 13 families worldwide revealed a shared pattern of developmental and cognitive delay, movement abnormalities, and defects of the corpus callosum, the structure connecting the two halves of the brain. The disorder […]
Common Disease Genetics Field Watch: APOE4 Moves From Association Toward Mechanism in Alzheimer’s Disease
A study is shedding light on how APOE genetics may shape Alzheimer’s disease inside the brain. Researchers compared human astrocytes carrying APOE3 and APOE4 in chimeric mouse models. They found that APOE genotype can influence not only astrocyte behavior, but also Alzheimer-related pathology and microglial responses. The results point to a more specific disease mechanism […]
CACNA1C variants associated with focal epilepsy and their correlations with arrhythmias and developmental disorders (Contributed by Dr Chuan-Fang Cheng)
CACNA1C is known to be associated with arrhythmias and developmental disorders, while its role in epilepsy has remained unclear. In this study, we focused on CACNA1C mutations in focal epilepsy, one of the most common seizure types. Using trio-based whole-exome sequencing, we identified three de novo CACNA1C mutations in patients with focal epilepsy. Notably, we […]
The British Society for Genetic Medicine guidance on managing incidental findings identified during rare disease genomic testing (Contributed by Dr Sian Ellard)
Genomic testing for people affected by rare diseases will occasionally identify a gene variant or other finding that is not related to the reason for testing. This guidance on managing such “incidental findings” has been developed to support the specialist genomics workforce within the national health services in the UK and Ireland. It describes the […]
Enrichment of an Ehlers-Danlos-like Phenotype in Women with the FMR1 Premutation: A Pilot Study (Contributed by Dr Emily L Casanova)
Women who carry the FMR1 premutation are known to be at risk for several fragile X-associated conditions, but connective tissue problems have received relatively little attention. In this pilot study, we found that women with the premutation were much more likely than expected to show features resembling hypermobile Ehlers-Danlos syndrome, including joint hypermobility, chronic pain, […]
Everolimus for the treatment of neuropsychological deficits in tuberous sclerosis complex: findings from the TRON multicentre randomised controlled trial (Contributed by Dr Julian R Sampson)
Tuberous sclerosis complex is a rare inherited condition that causes a combination of widespread tumours, epilepsy and neuropsychological problems including autism and learning difficulties. Everolimus is an effective drug for treating the tumours and epilepsy. This paper reports a clinical trial of twenty-four weeks of everolimus treatment compared with placebo (an identical appearing pill without […]
Single-cell transcriptomics identifies neural fate disruption and glial reprogramming caused by RARS2 deficiency (Contributed by Dr. Xing Wei)
Pontocerebellar hypoplasia type 6 is a severe childhood brain disorder caused by defects in genes important for mitochondrial function. In this study, we used zebrafish and single-cell RNA sequencing to understand how loss of RARS2 affects early brain development. We found that RARS2 deficiency damages mitochondrial structure, disrupts normal neuronal development, and promotes abnormal glial […]
Field watch: Human body single-cell atlas of three-dimensional genome organization and DNA methylation
A study published in Science presents a single-cell atlas of DNA methylation and three-dimensional genome organization across the human body. Zhou and colleagues profiled 86,689 nuclei from 16 adult tissues, characterizing 35 major cell types and 206 subtypes. Their findings reveal extensive cell type–specific differences in methylation, chromatin loops, and long-range genome organization, while showing […]
Potential advantage of clinical exome sequencing in BRCA1/2-negative families: a retrospective study of a cohort of 500 patients at a high-risk for hereditary cancers (Contributed by Dr. Federico Anaclerio)
Many families with a strong history of cancer remain without a genetic diagnosis after standard BRCA1/2 testing. In this study, we investigated whether Clinical Exome Sequencing (CES) could provide additional genomic information in 500 high-risk individuals who previously tested negative for BRCA1/2 pathogenic variants. While most additional findings are not yet ready for routine clinical […]