Newly Discovered Gene Mutation is Linked to Hereditary Deafness
Researchers led by geneticists at the Miller School have discovered a new gene mutation that causes hearing loss. Their study, which focused on a large Turkish family in which six individuals have been affected by hereditary deafness, identified a mutated form of the gene FAM65B as a cause of sensorineural hearing loss.
The research also demonstrates that FAM65B is a previously unrecognized component of the inner ear that is required for hearing. Their report, “FAM65B is a membrane-associated protein of hair cell stereocilia required for hearing,” was published online by the Proceedings of the National Academy of Sciences.
The study was led by Mustafa Tekin, M.D., professor of human genetics at the Dr. John T. Macdonald Foundation Department of Human Genetics. Oscar Diaz-Horta, Ph.D., a postdoctoral fellow at the John P. Hussman Institute for Human Genomics, was first author of the study.
“Hearing loss is the most common human sensory problem,” said Tekin. “We hope that identifying a new genetic cause of this disorder will lead to a better understanding of the molecular components of normal hearing.”
Hearing loss, which affects approximately 1 in 500 newborns, most often results from mutations of single genes that perform specific functions in the inner ear, where sound waves are converted to electrical signals. This process originates in the stereocilia — “hairs” projecting from cochlear hair cells that interconnect to form the hair bundle. Most of the approximately 50 previously identified hair bundle proteins are the products of genes that, when mutated, lead to hearing loss.
Researchers in this study, who conducted a genetic analysis of the subject family, identified a mutated form of FAM65B — a protein previously unassociated with hearing — as the cause. Further characterization of the protein product of FAM65B in rodents and zebrafish has confirmed the findings of the family study.
The study is an outcome of a longstanding collaboration among different departments at UM. Other UM researchers included Zhongmin (John) Lu, Ph.D., associate professor of biology; Katherina Walz, Ph.D., research assistant professor of human genetics and medicine; Amjad Farooq, Ph.D., assistant professor of biochemistry and molecular biology; Xue Z. Liu, M.D., Ph.D., professor of otolaryngology, human genetics and pediatrics; and Susan Blanton, Ph.D., associate professor of human genetics and neurology.
Additional researchers at the John P. Hussman Institute for Human Genomics included Clemer Abad, research associate; Guney Bademci, M.D., assistant scientist; Lei Cao, Ph.D. candidate; and Joseph Foster, B.S., research associate. Additional researchers in the Department of Otolaryngology included M’hamed Grati, Ph.D., associate scientist and principal investigator; and Rahul Mittal, Ph.D., research associate.
FAM65B is the fourth deafness gene identified through Tekin’s NIH grant R01DC009645.