Long-read genome sequencing improves detection and functional interpretation of structural and repeat variants in autism
Cell Genom. 2026 Mar 9:101186. doi: 10.1016/j.xgen.2026.101186. Online ahead of print. ABSTRACT Long-read whole-genome sequencing (LR-WGS) technologies enhance the discovery of structural variants (SVs) and tandem repeats (TRs). We performed LR-WGS on 267 individuals from 63 autism spectrum disorder (ASD) families and generated an integrated call set combining long- and short-read data. LR-WGS increased detection […]
Saturation editing of RNU4-2 reveals distinct dominant and recessive disorders
Nature. 2026 Apr 8. doi: 10.1038/s41586-026-10334-9. Online ahead of print. ABSTRACT Recently, de novo variants in an 18-nucleotide region in the centre of RNU4-2 were shown to cause ReNU syndrome, a syndromic neurodevelopmental disorder that is predicted to affect tens of thousands of individuals worldwide1,2. RNU4-2 is a non-protein-coding gene that is transcribed into the […]
Disease insights from brain somatic mosaicism
Exp Mol Med. 2026 Apr 8. doi: 10.1038/s12276-024-01331-x. Online ahead of print. ABSTRACT Brain somatic mosaicism (BSM) refers to genome variation within brain cells that results from accumulated postzygotic mutations. These mutations can be used to understand cell lineage, molecular dynamics and disease processes. Unlike most other organs, brain cells are mostly fixed in position […]
Systematic analysis of snRNA genes reveals frequent RNU2-2 variants in dominant and recessive developmental and epileptic encephalopathies
Nat Genet. 2026 Mar 30. doi: 10.1038/s41588-026-02547-5. Online ahead of print. ABSTRACT Small nuclear RNAs (snRNAs) are essential components of the spliceosome. De novo variants in snRNA genes RNU4-2 (ReNU syndrome), RNU5B-1 and RNU2-2 have been linked to dominant neurodevelopmental disorders (NDDs), revealing a large unexpected contribution of noncoding RNA genes to genetic diseases. Here, […]
Developmental organization of sensory and sympathetic ganglia
Nature. 2026 Apr 1. doi: 10.1038/s41586-026-10313-0. Online ahead of print. ABSTRACT The neural crest generates a broad spectrum of cell types that migrate across the body plan to populate multiple tissues1. However, the relationship between lineages of neural crest derivatives remains unclear, and the extent to which neural crest cells delaminated from the neural tube […]
When loss is gain: truncating mutations in additional sex combs (ASXL) gene family in cancer and neurodevelopment
Trends Genet. 2026 Mar 31:S0168-9525(26)00038-7. doi: 10.1016/j.tig.2026.02.003. Online ahead of print. ABSTRACT The human ASXL gene family consists of ASXL1, ASXL2, and ASXL3, first described as the additional sex combs (Asx) in Drosophila. The encoded proteins scaffold BAP1-mediated histone H2A deubiquitination. ASXL genes are implicated in pre-cancerous, cancerous, and neurodevelopmental conditions. Truncating mutations predominate and […]
De novo mutations and environmental modifiers: lessons from neural tube defects
Trends Genet. 2026 Mar 18:S0168-9525(26)00030-2. doi: 10.1016/j.tig.2026.01.011. Online ahead of print. ABSTRACT Spina bifida is a clinically and etiologically heterogeneous group of neural tube defects (NTDs) that includes meningomyelocele. While folic acid (FA) supplementation has reduced the incidence by 30-50%, genetic contributors remain only partially understood. New trio sequencing technology has identified de novo mutations […]
Recessive Loss of DIAPH1 Function Causes a Progressive Neurodevelopmental Syndrome with Variable Immunological Involvement
Genet Med. 2026 Mar 16:102551. doi: 10.1016/j.gim.2026.102551. Online ahead of print. ABSTRACT PURPOSE: Biallelic DIAPH1 pathogenic variants cause a neurodevelopmental syndrome occasionally associated with immunodeficiency. This study aims to define the clinical and immunological spectrum of DIAPH1-related neuroimmunological syndrome and explore the gene’s developmental role using vertebrate models. METHODS: 53 individuals with biallelic DIAPH1 variants, […]
Genetic Variation in Clinical Cohorts
N Engl J Med. 2026 Mar 12;394(11):1142. doi: 10.1056/NEJMc2518638. NO ABSTRACT PMID:41812208 | DOI:10.1056/NEJMc2518638
Expanding the phenotypic and immunological landscape of Alazami syndrome: Evidence from seven new patients with LARP7 gene variants
Eur J Pediatr. 2026 Mar 11;185(4):175. doi: 10.1007/s00431-026-06801-0. ABSTRACT Alazami syndrome is a neurodevelopmental disorder characterized by postnatal growth retardation, moderate to severe intellectual disability, and facial dysmorphology. It is caused by biallelic variants in the transcriptional regulator La ribonucleoprotein 7 (LARP7), where frameshift variants accounted for the majority of cases. The current study presents […]