CohesinMutationen

Cohesin mutations refer to genetic alterations in the *COHESIN* complex, a multi-subunit protein ring structure essential for chromosome dynamics during cell division. The cohesin complex plays a critical role in maintaining sister chromatid cohesion, facilitating proper chromosome segregation, and regulating gene expression through chromatin organization. Mutations in cohesin-related genes have been linked to a spectrum of developmental disorders and cancers.

The primary components of the cohesin complex include the core subunits RAD21, SMC1A, SMC3, and STAG1/STAG2, along with accessory proteins like SCC1 (RAD21), PDS5A/B, and WAPL. Disruptions in these genes can impair cohesin function, leading to chromosomal instability, abnormal cell proliferation, and developmental abnormalities. For instance, mutations in *SMC1A* and *SMC3* are associated with the Cornelia de Lange syndrome (CdLS), a rare genetic disorder characterized by intellectual disability, growth retardation, and distinctive facial features.

Beyond developmental disorders, cohesin mutations have also been implicated in cancer. Altered cohesin activity can contribute to genomic rearrangements, such as translocations and deletions, which drive tumorigenesis. For example, mutations in *STAG2*, a cohesin subunit, are frequently observed in various cancers, including breast, ovarian, and colorectal cancers, where they promote chromosomal instability and tumor progression.

Diagnosis of cohesin-related disorders often involves genetic testing, such as whole-exome sequencing or targeted gene panels, to identify pathogenic variants. Treatment approaches are largely supportive, focusing on managing symptoms associated with developmental disorders, while cancer-related mutations may be targeted through emerging therapies aimed at stabilizing chromosomal integrity or inhibiting oncogenic pathways. Research into cohesin biology continues to uncover new therapeutic opportunities, particularly in precision oncology.