News : 2019 : January

UM Researchers Discover New Genetic Cause of Deafness

New Genetic Cause of Deafness

Hearing loss is the most common sensory deficit worldwide. There is, however, a great deal that is still unknown about its causes.

When parents are told their children are deaf or hard of hearing, they often have many questions – and one of the most common questions is “Why?”

“In over half of infants affected by hearing loss, genetic factors are involved,” said Dr. Mustafa Tekin, a Professor in the Dr. John T. Macdonald Foundation Department of Human Genetics and a member of the John P. Hussman Institute for Human Genomics at the University of Miami Miller School of Medicine, where he also serves as Chief of the Clinical and Translational Genetics Division. “To date, we know of over 100 genes that are linked to deafness. But they can explain only about half of cases with hearing loss.”

A study by University of Miami researchers and scientists at institutions in Turkey and China, led by Dr. Tekin, has recently revealed that a mutation in the Grb-2-related adaptor protein (GRAP) gene is linked to hearing loss in people and fruit flies.

The defect in the GRAP gene has been found in two unrelated Turkish families. Dr. Grace Zhai, an Associate Professor in the Department of Molecular and Cellular Pharmacology, conducted studies on the fruit fly counterpart of GRAP called drk. Flies with mutant drk were unable to detect gravity and keep their balance, which was due to defects in their hearing organ. Importantly, the normal human GRAP (but not the mutant form) can restore the sensory function of the drk mutant flies. The findings support the deleterious nature of the mutant GRAP identified from patients with hearing loss.

“We have not just found a new genetic cause of deafness,” said Dr. Tekin. “This study also unveils a gene playing a fundamental role in hearing in different species, which will inform future research on therapeutic targets.”

Currently, there are no cures for hearing loss. Symptoms are often treated with hearing aids or cochlear implants.

The article on the GRAP gene’s role as a genetic cause of deafness was published in the Proceedings of the National Academy of Sciences (PNAS), one of the world’s most-cited and comprehensive multidisciplinary scientific journals, on January 4, 2019.

Other collaborators on this study include, among others, Drs. Chong Li and Guney Bademci (co-first authors), and Oscar Diaz-Horta, Yi Zhu, Timothy Gavin Mitchell, Clemer Abad, Serhat Seyhan, Filiz Basak Cengiz, Susan H. Blanton, Amjad Farooq, and Katherina Walz at the University of Miami.

Journal article:
Li C, Bademci G, Subasioglu A, Diaz-Horta O, Zhu Y, Liu J, Mitchell TG, Abad C, Seyhan S, Duman D, Cengiz FB, Tokgoz-Yilmaz S, Blanton SH, Farooq A, Walz K, Zhai RG, Tekin M. Dysfunction of GRAP, encoding the GRB2-related adaptor protein, is linked to sensorineural hearing loss. Proc Natl Acad Sci U S A. 2019 Jan 4. pii: 201810951. doi: 10.1073/pnas.1810951116. [Epub ahead of print] PubMed PMID: 30610177.