ArticleGenetics in medicine : official journal of the American College of Medical Genetics2022
Variants in ADD1 cause intellectual disability, corpus callosum dysgenesis, and ventriculomegaly in humans.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 16 citations in OpenAlex.
- Missense variants in DPYSL5 associated with neurodevelopmental disorders and brain malformations cause impaired neuronal maturation in vitro.Molecular psychiatry · 2026Article
- Convergence and divergence of genes informed by common and rare variants of autism spectrum disorders in tissue-specific pathways and gene networks.Translational psychiatry · 2026Article
- Histone phosphorylation analysis of two main TCM syndromes of chronic fatigue syndrome.Journal of translational medicine · 2025Article
- Dynamic changes in mRNA isoform usage during human retinal development.bioRxiv : the preprint server for biology · 2025Article
- Article
- Autism candidate genebioRxiv : the preprint server for biology · 2024Article
- Single-cell long-read sequencing in human cerebral organoids uncovers cell-type-specific and autism-associated exons.Cell reports · 2023Article
- Epilepsies of presumed genetic etiology show enrichment of rare variants that occur in the general population.American journal of human genetics · 2023Article
- The role of rare genetic variants enrichment in epilepsies of presumed genetic etiology.medRxiv : the preprint server for health sciences · 2023Article
- Contribution of the dihydropyrimidinase-like proteins family in synaptic physiology and in neurodevelopmental disorders.Frontiers in neuroscience · 2023Review
- Molecular mechanisms of synaptogenesis.Frontiers in synaptic neuroscience · 2022Review
Corrections and comments
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Authors and funding
26 authors at 9 institutions in 4 countries.
Funding
Abstract
purposeAdducins interconnect spectrin and actin filaments to form polygonal scaffolds beneath the cell membranes and form ring-like structures in neuronal axons. Adducins regulate mouse neural development, but their function in the human brain is unknown.
methodsWe used exome sequencing to uncover ADD1 variants associated with intellectual disability (ID) and brain malformations. We studied ADD1 splice isoforms in mouse and human neocortex development with RNA sequencing, super resolution imaging, and immunoblotting. We investigated 4 variant ADD1 proteins and heterozygous ADD1 cells for protein expression and ADD1-ADD2 dimerization. We studied Add1 functions in vivo using Add1 knockout mice.
resultsWe uncovered loss-of-function ADD1 variants in 4 unrelated individuals affected by ID and/or structural brain defects. Three additional de novo copy number variations covering the ADD1 locus were associated with ID and brain malformations. ADD1 is highly expressed in the neocortex and the corpus callosum, whereas ADD1 splice isoforms are dynamically expressed between cortical progenitors and postmitotic neurons. Human variants impair ADD1 protein expression and/or dimerization with ADD2. Add1 knockout mice recapitulate corpus callosum dysgenesis and ventriculomegaly phenotypes.
conclusionOur human and mouse genetics results indicate that pathogenic ADD1 variants cause corpus callosum dysgenesis, ventriculomegaly, and/or ID.
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