Genetic Discovery Links CRNKL1 to Rare Childhood Brain Disorder

Researchers from the University of Otago–Ōtākou Whakaihu Waka have uncovered a significant genetic cause behind a rare and severe developmental disorder affecting children’s brain growth and function. This groundbreaking study, recently published in the American Journal of Human Genetics, focuses on specific genetic alterations in the CRNKL1 gene. The findings provide crucial insights into how disruptions in genetic splicing processes can lead to profound neurodevelopmental impairments.

The research team examined 10 families affected by a disorder characterized by extreme microcephaly (small head size), pontocerebellar hypoplasia (underdevelopment of the brain stem and cerebellum), seizures, and intellectual disability. Notably, nine of these families shared identical genetic mutations within the CRNKL1 gene, pinpointing this gene’s critical role in brain development.

Associate Professor Louise Bicknell, from Otago’s Department of Biochemistry, explained that the body relies on precise genetic splicing to interpret instructions from DNA, which is essential for proper cellular function. Disruptions in this process, especially in the machinery that manages splicing, can have severe impacts on tissue development, particularly in the brain.

The discovery started with local efforts to help New Zealand families understand their children’s genetic conditions. Through international collaborations, the researchers identified similar mutations in families abroad, strengthening the evidence that alterations in CRNKL1 cause this disorder. The study revealed that all affected children exhibited severe physical and neurological features, correlating strongly with the specific mutations.

Dr. Sankalita Ray Das, the principal author, emphasized that CRNKL1 plays an indispensable role in normal brain formation. The research highlights the intricate and highly specialized functions of parts of the splicing machinery. These insights not only identify a new genetic cause for this devastating condition but also deepen our understanding of the molecular pathways involved in brain development.

This research offers hope for affected families and sets a foundation for future studies aimed at unlocking the complexities of genetic influences on neurodevelopmental disorders. It also underscores the importance of genetic screening and early diagnosis to better understand and potentially address similar conditions in the future.

Source: https://medicalxpress.com/news/2025-06-genetic-rare-childhood-brain-developmental.html