New Research on AFF3 Gene Sheds Light on Rare Developmental Disorder

Friday - May 31 2024, 02:08 UTC - 5 months ago

New research has shown that both the excess and deficiency of the AFF3 protein can lead to a rare genetic disorder called KINSSHIP syndrome. The study confirms the critical role of this gene in embryonic development and provides a necessary foundation for early and accurate diagnosis of the disorder. Collaborating with researchers from nine different countries, the team identified 21 individuals with a deficiency of the AFF3 gene, further supporting their hypothesis.

New research has shed light on a rare genetic disease caused by mutations in the AFF3 gene. Led by genetic expert Alexandre Reymond, a team of scientists from the Center for Integrative Genomics (CIG) and the Faculty of Biology and Medicine (FBM) at the University of Lausanne (UNIL) have made a major step forward in the early detection of KINSSHIP syndrome. Published in Genome Medicine, the study reveals that both the accumulation and deficiency of the AFF3 protein can severely impact development .

KINSSHIP syndrome is a rare condition affecting about thirty individuals worldwide. It is characterized by intellectual disability, an increased risk of epilepsy, kidney malformations, and bone deformations in affected children. Due to the limited number of documented cases, the understanding and diagnosis of this disorder have been challenging.In 2021, the research team discovered the link between mutations in the AFF3 gene and KINSSHIP syndrome .

They found that an abnormal accumulation of the AFF3 protein was the leading cause of the disorder. However, they also noticed that individuals with a deficiency of this same protein exhibited similar symptoms.To test their hypothesis, the scientists used data from the gnomAD database, which contains genome sequences from hundreds of thousands of unrelated people. By analyzing the available data on AFF3 mutations, they found that loss-of-function mutations in this gene are rare, indicating their harmful nature and critical role in the body .

Collaborating with researchers from nine different countries, the team identified 21 patients with only one copy of the AFF3 gene, instead of the two normally present in the human genome. These individuals displayed similar but less severe symptoms than those of KINSSHIP syndrome, providing further evidence that both an excess and deficiency of the AFF3 protein can lead to developmental issues.To validate their findings, the researchers conducted experiments on cells of patients, mice, and zebrafish .

They artificially decreased and increased the amount of AFF3 protein in zebrafish eggs, resulting in significant developmental defects in the resulting embryos. This confirmed that precise levels of AFF3 are essential for proper embryonic development.In conclusion, the authors' research offers critical insights for early diagnosis of KINSSHIP syndrome and other rare disorders caused by mutations in the AFF3 gene .

Their findings allow for better understanding and potential treatment of this condition, ultimately improving the quality of life for those affected.