New DIAL Syndrome Identified: Linking DNA Repair Defects to Childhood Cancer and Chemotherapy Response

Researchers have identified a novel hereditary disorder called DIAL syndrome that significantly impacts DNA repair mechanisms in cells. This discovery, published in Nature Communications, highlights how mutations in the DIAPH1 gene compromise the body's ability to repair DNA damage effectively. The DIAPH1 gene encodes a protein crucial for facilitating DNA repair by promoting the formation of actin, which acts like a scaffolding around DNA breaks to promote accurate repair processes.

Children with DIAL syndrome often exhibit symptoms resembling other chromosome breakage disorders early in life. The condition is characterized by an increased risk of developing B-cell lymphoma due to the impaired regulation of B cell development. Moreover, because cancer treatments such as radiotherapy and chemotherapy cause DNA damage to eliminate cancer cells, individuals with DIAL syndrome are particularly vulnerable. Their cells' inability to repair this damage can lead to dangerous side effects and hinder treatment effectiveness.

The research team, led by experts from the University of Birmingham and collaborating with University College London, analyzed cells from a patient who had symptoms similar to DNA repair deficiencies for over 19 years. This long-term case was pivotal in recognizing DIAL syndrome as a distinct condition. They further identified mutations in the DIAPH1 gene in 32 additional patients, confirming the syndrome's existence and shedding light on its genetic basis.

Professor Grant Stewart emphasized the importance of early diagnosis, stating that identifying children with such DNA repair deficiencies before cancer treatments can help tailor safer and more effective therapy plans. The team aims to include DIAL syndrome in genetic screening panels for newborns, enabling earlier diagnosis and personalized management. Their ongoing work involves developing biomarkers and potential targeted therapies to mitigate the effects of this condition.

This breakthrough not only offers crucial insights for affected families but also guides clinicians in adjusting treatment approaches to minimize adverse effects, ultimately improving patient outcomes. As research progresses, better understanding and intervention strategies are expected to evolve, enhancing care for patients with rare genetic syndromes like DIAL.

Source: https://medicalxpress.com/news/2025-06-discovery-dial-syndrome-links-faulty.html