Discovering novel genes and pathomechanisms underlying rare neurodevelopmental disorders in Pakistan

Summary

The complexity and rarity of inherited brain disorders poses a major global challenge for modern medicine. These disorders are associated with significant healthcare and financial burdens, particularly in lower income countries with more limited access to cutting-edge clinical-genetic services. However, the unique population characteristics of Pakistani communities offers an opportunity to identify the genetic causes of disease as well as discover disorders new to medical science.

What are we doing?

We are investigating the spectrum and causes of rare genetic brain disorders in Pakistani communities to help us understand them, discover new genetic conditions, and learn about the processes that are important for normal brain development. Our research will also benefit healthcare provision in medically underserved communities by improving diagnosis, clinical management, and treatment for Pakistani families and families with these conditions globally.

How are we doing it?

By developing strong, long-term collaborative partnerships with Pakistani clinical-genetic research groups we will recruit around 100 Pakistani families with multiple members affected by rare brain disorders. We’ll use our internationally renowned clinical, genomic and bioinformatic expertise to pinpoint genetic variations causing neurogenetic disorders affecting Pakistani families and, through international collaboration, identify other families worldwide with the same genetic conditions to help us better understand these diseases.

What happens next?

Alongside genetic studies of the recruited families, initial investigations will focus on clinical, genetic and molecular studies of two likely new brain developmental disorders recently identified in Pakistani families as part of pilot data for this project. This will confirm both genes as novel genetic diseases and form an excellent foundation for further study. We’ll share these findings with clinical care teams in Pakistan and globally to enhance clinical management and understanding of these conditions worldwide.

In the longer term, we hope that cell and molecular studies of new genetic conditions, discovered in collaboration with local and global experts, will provide important new insights into disease mechanisms and explore potential treatments. As part of this work, we will host international PhD student exchanges with Pakistani research centres for training within the Exeter Rare Disease Genomics Group.