Document Type
Article
Publication Date
3-30-2026
Identifier
DOI: 10.1038/s41467-026-71177-6; PMCID: PMC13035837
Abstract
The role of the cohesin complex depends on the cohesin loader proteins NIPBL and MAU2. While NIPBL variants are a major cause of Cornelia de Lange Syndrome (CdLS), the role of MAU2 in disease is unclear. We describe 18 individuals carrying 15 heterozygous MAU2 variants and demonstrate pathogenicity through functional analyses. In-frame MAU2 variants predominantly impair NIPBL-MAU2 interaction, whereas truncating variants cause MAU2 haploinsufficiency and lead to NIPBL reduction. Most individuals exhibit a DNA methylation profile compatible with the CdLS episignature. We also describe two MAU2-specific episignatures that reflect variant-dependent molecular consequences. Affected individuals display a wide range of phenotypes, from classic CdLS to milder presentations, with short stature and microcephaly as major features. A heterozygous Mau2 knockout mouse model recapitulates these traits, confirming the causal role of MAU2 disruption in vivo. Our study establishes MAU2 as a CdLS-associated gene and delineates a MAU2-related chromatinopathy with variable expressivity.
Journal Title
Nat Commun
Volume
17
Issue
1
MeSH Keywords
De Lange Syndrome; Humans; Animals; Cell Cycle Proteins; Male; Female; Cohesins; Mice; Mice, Knockout; Haploinsufficiency; Chromosomal Proteins, Non-Histone; DNA Methylation; Child; Phenotype; Heterozygote; Adolescent; Child, Preschool; Pedigree
PubMed ID
41912533
Keywords
De Lange Syndrome; Cell Cycle Proteins; Cohesins; Knockout Mice; Haploinsufficiency; Non-Histone Chromosomal Proteins; DNA Methylation; Phenotype; Heterozygote; Pedigree
Recommended Citation
Parenti I, Hesters A, Gil-Salvador M, et al. Pathogenic variants in the cohesin loader subunit MAU2 underlie a distinct Cornelia de Lange Syndrome subtype. Nat Commun. 2026;17(1):3036. Published 2026 Mar 30. doi:10.1038/s41467-026-71177-6
Comments
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Publisher's Link: https://www.nature.com/articles/s41467-026-71177-6