A recent study has identified rare variants in the YKT6 gene as the cause of a new neurological disorder that results in developmental delays and severe progressive liver disease, posing a potential risk for liver cancer as well. Led by Dr. Hugo Bellen and Dr. Wendy Chung, the study published in Genetics in Medicine sheds light on the previously unknown genetic disorder. The YKT6 gene, known for its role in intracellular vesicular trafficking, is now linked to this new disease, prompting further research into understanding and treating it in the future.
Collaborating with researchers and clinicians from various institutions, the team identified three unrelated individuals with missense variants in both copies of the YKT6 gene. These individuals exhibited early-onset symptoms, including failure to thrive, developmental delays, and neurological defects. Notably, two of them also experienced liver dysfunction, suggesting a link between the YKT6 gene variants and liver-related complications. The study also highlighted a common ancestral variant present in the Syrian/Saint Thomas Christian community of Kerala, India, indicating a potential genetic lineage within the affected population.
Further investigation into the YKT6 gene revealed its role in impairing autophagy, a critical cellular process for degrading and recycling proteins and other molecules. Using fruit flies as a model, researchers found that various YKT6 variants led to different levels of defects, with some causing severe impairment in lifespan and locomotion. The study emphasized the importance of understanding how these variants affect the autophagy pathway, ultimately contributing to the disease pathology observed in affected individuals.
Based on their findings, the researchers recommended the inclusion of the YKT6 gene in carrier screenings within the Syrian/Saint Thomas Christian community to identify individuals at risk for the related disorder. Additionally, they suggested screening children diagnosed with YKT6 liver disease for hepatocellular carcinoma, emphasizing the need for comprehensive medical monitoring and management for affected individuals. While the study offers valuable insights into the genetic basis of this novel disorder, more research with larger patient cohorts is necessary to fully understand its pathogenesis and identify potential therapeutic targets.
Supported by various funding sources, including the National Institutes of Health, the study represents a collaborative effort to unravel the genetic underpinnings of the newly discovered neurological disorder associated with YKT6 gene variants. Through extensive genetic analysis, experimental studies, and clinical observations, the researchers aim to advance the understanding of this condition and pave the way for future treatments and interventions that may benefit affected individuals and their families.
