Di Nardo Maddalena, Krantz Ian D, Musio Antonio
Institute for Biomedical Technologies, National Research Council, 56124 Pisa, Italy.
Roberts Individualized Medical Genetics Center, Division of Human Genetics, The Department of Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104-4318, USA.
Cells. 2024 Dec 7;13(23):2025. doi: 10.3390/cells13232025.
Cornelia de Lange syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder. Pathogenic variants in genes encoding the structural subunits and regulatory proteins of the cohesin complex (, , , , and ) are the primary contributors to the pathogenesis of CdLS. Pathogenic variations in these genes disrupt normal cohesin function, leading to the syndrome's diverse and complex clinical presentation. In this study, we discovered that cells harboring variants in the , and genes exhibit spontaneous genome instability, elevated oxidative stress and premature cellular aging. These findings suggest that cohesin plays a critical role in maintaining proper cellular function and highlight its contribution to the pathophysiology seen in the related diagnoses.
科妮莉亚·德朗格综合征（CdLS）是一种罕见的、显性遗传的多系统发育障碍。编码黏连蛋白复合体结构亚基和调节蛋白的基因（、、、和）中的致病变异是CdLS发病机制的主要因素。这些基因中的致病变异破坏了正常的黏连蛋白功能，导致该综合征多样且复杂的临床表现。在本研究中，我们发现携带、和基因变异的细胞表现出自发性基因组不稳定、氧化应激升高和细胞早衰。这些发现表明黏连蛋白在维持细胞正常功能中起关键作用，并突出了其在相关诊断中所见病理生理学中的作用。
