Department of Nephrology, Anhui Provincial Children's Hospital, Hefei, China.
Mol Genet Genomic Med. 2024 Jan;12(1):e2318. doi: 10.1002/mgg3.2318. Epub 2023 Nov 14.
Cornelia 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.
We 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).
The 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.
We 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.
Cornelia de Lange 综合征（CdLS）主要表现为特定的面部特征、生长迟缓以及骨骼畸形。据报道，有七个基因可导致 CdLS。最近的研究表明，影响黏连蛋白复合物调节因子 MAU2 的失活变异也可导致 CdLS。迄今为止，全世界仅报告了一例 MAU2-CdLS 病例。
我们在一位 CdLS 中国患者中检测到 MAU2 基因 NM_015329 的新型变异，c.526C>T（p.Arg176Trp），构建了体外转录和蛋白水平分析的质粒，并使用分子动力学（MD）分析了 MAU2/NIPBL 复合物的相互作用。
结果表明，与外源性野生型蛋白相比，外源性 MAU2 突变蛋白的水平明显降低。然而，MD 分析预测 MAU2 和 NIPBL 蛋白之间的结合自由能增加，这可能影响复合物的结构稳定性。
我们对一个中国家族的 MAU2-CdLS 病例进行了研究，这加强了 MAU2 变异与 CdLS 表型之间的关联。因此，我们建议将 MAU2 纳入 CdLS 基因筛查列表中。
