Researchers from the John T. Macdonald Department of Human Genetics and the John P. Hussman Institute for Human Genomics at the University of Miami Miller School of Medicine have discovered that hereditary mutations in the MINAR2 gene caused deafness in four families. The gene variation mainly affects the hair cells of the inner ear, which are essential for hearing. The authors believe that the progressive nature of this hearing loss, in some affected individuals and in mice, could provide opportunities for treatment. The study titled “Mutations in MINAR2 encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice” was published online in the magazine on June 21 PNAS†
MINAR2 plays an important role in hearing and these hereditary mutations lead to sensorineural deafness. The findings suggest that these cases may be suitable for intervention with genetic therapies.”
Mustafa Tekin, MD, Professor, Dr. John T. Macdonald Foundation Department of Human Genetics and senior author on the paper
dr. Tekin has been studying the genetic basis behind hearing loss for more than 20 years and has built a biorepository containing a genomic sequencing database of deafness-associated gene mutations in families around the world.
“We look first at known mutations in genes,” said Dr. tekin. “If we don’t find one, we do whole genome sequencing to potentially identify new genes or something we may have missed in the first test.”
In this study, the team sequenced the genome of a Turkish family targeting known deafness genes, but found nothing. After whole genome sequencing, they found DNA variants in MINAR2, which had only recently been described in the research literature. Scientists are still filling in the blanks about the gene’s function.
After identifying the variations in MINAR2 in one family, Dr. Tekin their database and found a second family with a different mutation in the same gene. Further investigation confirmed their findings in animal studies and identified three different MINAR2 mutations, which caused deafness in 13 people from four families.
“We found that this gene performs an important function,” says Dr. tekin. “The protein localizes to hair cells and other areas critical to hearing. Future research will focus on clarifying the gene’s role.”
Hair cells convert sound into electrical signals, which are then sent to the brain. When children are born deaf, they normally have few or no living hair cells. As a result, gene therapies and other regenerative efforts would likely fail. In ‘s mouse knockout model MINAR2, hair cells remain alive until later in life. This gradual hearing loss may require treatment.
“What’s surprising and promising for potential intervention is that, when we looked at the hair cells in our mouse model, they were alive to a certain age,” Tekin said. “That gives us a chance to provide treatment. We can insert the normal gene and potentially restore hearing.”
University of Miami Miller School of Medicine
Almonds, G., et al. (2022) Mutations in MINAR2-encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice. PNAS. doi.org/10.1073/pnas.2204084119.