Hearing loss before a child learns to speak can influence language development, schooling, communication and family decisions from the earliest years of life.

For families, an accurate diagnosis can help them understand whether deafness is likely to occur in future children, whether it may be linked to other health issues and what forms of support or treatment are available. This is especially important in regions where inherited forms of deafness are more common, but genetic data is limited. Without such data, doctors might not be able to determine the cause of the impairment or anticipate the implications of the diagnosis later in life.

In the study “Genetics of prelingual isolated deafness and Usher syndrome in the Maghreb and Jordan: Harnessing the potential of homozygosity,” published in PNAS, Dr. Eliane Chouery, professor and genetics discipline co-coordinator in the Department of Human Genetics at the Gilbert and Rose-Marie Chagoury School of Medicine, contributed with international co-authors to a major analysis of inherited deafness in Tunisia, Jordan, Algeria, Morocco and Mauritania.

This work forms part of a broader research effort pioneered by the department to understand the genetic basis of hearing impairment, from studies of deafness in Lebanon to wider investigations of specific genes involved in hearing loss.

The researchers studied 450 unrelated patients from families with severe-to-profound bilateral hearing impairment that began before language development. They used a targeted genetic test covering 157 known deafness genes and compared results with the family’s medical history, clinical examinations and, where relevant, eye examinations and protein-structure predictions to better understand the effect of specific mutations.

The study found that inherited deafness in the cohort was highly diagnosable, meaning that the researchers were often able to identify the genetic cause behind the condition. Recessive inheritance, where a child usually inherits two altered copies of a gene, one from each parent, accounted for 92 percent of cases. Dominant inheritance, where one altered copy can be enough to cause the condition, accounted for 8 percent. The test detected mutations in 92 percent of patients and fully solved 89 percent of all cases, finding sufficient genetic evidence to explain the patient’s deafness.

Among patients with recessive or recessive syndromic forms where hearing loss occurs alongside other health conditions, the test explained the cause of deafness in nearly 94 percent of cases. The researchers identified 211 mutations across 49 deafness genes, including 76 mutations that had not been reported before. Two genes, GJB2 and LRTOMT, explained 41.5 percent of all cases, while 10 genes together accounted for 81.1 percent. However, the exact mutations varied considerably between countries, indicating many private or local mutations rather than a shared regional pattern.

Another important result was the role of parental consanguinity, where the parents are biologically related and are more likely to carry the same rare inherited mutation. In families with recessive deafness or recessive syndromic deafness, 85 percent reported parental consanguinity, and 92 percent of solved recessive cases involved homozygous mutations, whereby the same mutation was present on both copies of a gene.

This allowed the team to study how certain mutations behave more clearly than is usually possible. The most clinically important finding concerned genes that can cause either isolated deafness or Usher syndrome type 1, a more severe condition that combines deafness with balance problems and early vision loss. The study showed that some mutations previously associated with isolated deafness can lead to Usher syndrome when paired with a loss-of-function mutation, which severely disrupts gene activity.

The findings also point to what could come next. According to Dr. Chouery, the study “highlights the importance of implementing preventive genetic counseling strategies and supports the feasibility of integrating genetic testing into newborn hearing screening programs in the region, allowing for earlier diagnosis and intervention.” This is particularly important as gene-based treatments for hereditary hearing impairment continue to advance. “Gene-based therapies for hereditary hearing impairment have emerged as one of the most promising advances in precision medicine,” she said.

One example is OTOF, a gene linked to autosomal recessive prelingual deafness and auditory neuropathy. Dr. Chouery noted that her team was among the first to describe the involvement of OTOF in this form of deafness, helping build the scientific basis for later therapeutic work. In 2026, the US Food and Drug Administration approved the first gene therapy for genetic hearing loss, targeting OTOF-associated severe-to-profound hearing loss.

“These advances clearly demonstrate that without accurately identifying and describing the causative mutation, effective treatment cannot be developed,” said Dr. Chouery. “Gene therapy approaches are mutation- and gene-specific, meaning that the therapeutic strategy depends directly on the underlying molecular defect identified in each patient or family.”

The study makes a strong case for collecting detailed genetic and clinical data from underrepresented populations. For families, such work can turn uncertainty into clearer guidance. For clinicians, it shows that accurate diagnosis depends not only on identifying a gene but on understanding the behavior of each mutation.

To browse more scholarly output by the LAU community, visit our open-access digital archive, the Lebanese American University Repository (LAUR).