In less than a year, the genetics team at LAU’s Gilbert and Rose-Marie Chagoury School of Medicine—comprising Dr. Andre Megarbane, assistant dean for research and department chair, and associate professors Dr. Cybel Mehawej and Dr. Eliane Chouery—has published another groundbreaking study on the POLD3 gene, a key player in DNA replication and repair that is associated with immunodeficiency and hearing impairment.

Featured in the October issue of the European Journal of Human Genetics, the research is the first to connect heterozygous variants— alterations affecting one of the two copies of a gene, each being inherited from a parent—in the POLD3 gene to gradual hearing decline and issues with balance in people over 40.

What prompted you to further explore POLD3’s connection with hearing impairment?

Our previous work related to POLD3, and published in Clinical Immunology in 2023, linked homozygous variants in this gene to immunodeficiency and congenital deafness. Interestingly, in that study, we observed that the parents who are heterozygous carriers developed hearing impairment in adulthood. This finding prompted us to evaluate whether heterozygous variants in POLD3 can be linked to adult-onset hearing impairment.

Based on previous international studies, we know that some genes can be involved in congenital hearing loss when mutated at a homozygous state, or in adult-onset milder forms of the disease in carriers with heterozygous variants.

This overlap between genetic conditions inspired us to further explore POLD3’s role in hearing impairment.

How do you see this discovery impacting the field of genetics and, ultimately, patient care?

This discovery adds POLD3 to the growing list of genes associated with hearing impairment, expanding our understanding of the genetic landscape of this condition.

Notably, we are the first to link hearing impairment to balance issues, which is significant because falls are a major concern in the elderly. By identifying POLD3’s role in both hearing loss and balance impairment, this finding opens new avenues for diagnosis and potentially targeted interventions.

In terms of patient care, early identification of individuals carrying POLD3 variants could lead to more personalized management strategies, especially for elderly individuals who are at increased risk of hearing loss and falls.

By addressing these issues together, we can help improve their overall quality of life and reduce fall-related damages.

How important was collaboration with other disciplines and international experts in achieving these findings?

Collaboration was absolutely essential for the success of this project. Our partnership with the University of Sheffield was particularly valuable, as their team helped us study the expression of POLD3 in the ears of mice, providing crucial insights into its role in hearing.

Additionally, the ENT specialists and audiologists at the LAU Medical Center–Rizk Hospital played a key role in designing the audiometry tests used to evaluate both hearing and balance impairments in our study. These collaborations allowed us to adopt a comprehensive approach, ensuring that we addressed both the clinical and genetic aspects of the research.

Such interdisciplinary and international collaborations are increasingly crucial in advancing complex genetic research, as they bring together diverse expertise to accelerate progress and deepen our understanding of genetic conditions.

In light of your discovery, how does it underscore the importance of genetic testing, and when do you recommend it should be conducted?

This discovery highlights the critical role of genetic testing in identifying individuals at risk for not only hearing loss but also balance-related issues, which could lead to falls in elderly populations.

We recommend genetic testing be conducted particularly for individuals with a family history of hearing impairment or balance issues, as early detection can inform interventions that improve quality of life.

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