Clinical study and genetic analysis of Cornelia de Lange syndrome caused by a novel MAU2 gene variant in a Chinese boy

Abstract

BackgroundCornelia de Lange syndrome (CdLS) is mainly characterized by specific facial features, growth retardation, and bone deformities. Seven genes reportedly cause CdLS. Recent research has reported that loss‐of‐function variants affecting MAU2, which encodes a regulator of the cohesin complex, can cause CdLS. Thus far, only one MAU2‐CdLS case has been reported worldwide.MethodsWe detected a novel variant in MAU2 gene, NM_015329, c.526C>T (p.Arg176Trp) in a Chinese patient with CdLS, constructed a plasmid for in vitro transcriptional and protein level analysis, and analyzed the interaction between the MAU2/NIPBL complex using molecular dynamics (MD).ResultsThe results showed that the level of the exogenous MAU2 mutant protein was significantly reduced compared with that of the exogenous wild‐type protein. However, MD analysis predicted an increased binding free energy between the MAU2 and NIPBL proteins that may impact the structural stability of the complex.ConclusionWe investigated a MAU2‐CdLS case in a Chinese family, which strengthens the association between MAU2 variants and CdLS phenotypes. We therefore propose that MAU2 be included in the CdLS gene screening list.

Advancing the Clinical and Molecular Understanding of Cornelia de Lange Syndrome: A Multidisciplinary Pediatric Case Series and Review of the Literature

“…It has been noted that the disease caused by MAU2 mutation may vary in presentation, with some patients showing classic CdLS symptoms. In contrast, others may have different conditions or additional genetic abnormalities [69].…”