Pathogenic variants in the cohesin loader subunit MAU2 underlie a distinct Cornelia de Lange Syndrome subtype - PubMed
4 hours ago
- #MAU2 variants
- #chromatinopathy
- #Cornelia de Lange Syndrome
- Pathogenic variants in the cohesin loader subunit MAU2 cause a distinct subtype of Cornelia de Lange Syndrome (CdLS).
- 18 individuals with 15 heterozygous MAU2 variants were studied; functional analyses confirmed pathogenicity.
- In-frame variants impair NIPBL-MAU2 interaction, while truncating variants cause MAU2 haploinsufficiency and NIPBL reduction.
- Most individuals show a DNA methylation profile consistent with the CdLS episignature, with two MAU2-specific episignatures identified.
- Phenotypes range from classic CdLS to milder presentations, with major features including short stature and microcephaly.
- A heterozygous Mau2 knockout mouse model recapitulates these traits, confirming MAU2 disruption as causal in vivo.
- The study establishes MAU2 as a CdLS-associated gene and delineates a MAU2-related chromatinopathy with variable expressivity.