New Gene Linked to Deafness in Humans, Mice

September 3, 2002

A newly discovered gene is responsible for one form of deafness in humans and mice, say two reports published this month by researchers supported by the National Institute on Deafness and Other Communication Disorders (NIDCD). The gene, dubbed TMIE (transmembrane inner ear expressed gene) in humans and Tmie in mice, is responsible for a genetic form of hearing loss that is not part of a syndrome--and therefore, not associated with other inherited characteristics, such as changes in skin or hair pigmentation--and that requires two copies of a mutant gene, one from each parent, to be expressed. To date, 15 genes have been identified that cause non-syndromic recessive hearing loss in humans.

The research shows that TMIE resides at locus DFNB6 in humans, a small stretch of chromosome 3 that is also home to other genes that have been linked to deafness. In mice, Tmie is located at the "spinner" locus, the site of a mutation on chromosome 9 that results in hearing loss and causes the mouse to spin around. Defects in Tmie result in inner ear problems for the mouse and are the cause of the spinner trait. The findings support a view currently held by geneticists involved in deafness research that the spinner mouse is a good model for studying non-syndromic hearing loss linked to the DFNB6 locus.

"These results demonstrate just how valuable communication can be within the research community, whether it's between two members of the same research team or between two colleagues grappling with similar problems," said Edward Wilcox, staff scientist in NIDCD's Laboratory of Molecular Genetics, Rockville, Md. When mouse researchers pinpointed Tmie at the spinner locus, they shared their results with the team studying human deafness, thus enabling them to zoom in on the region of the human chromosome that most closely corresponds to the region where Tmie occurs. "When NIDCD's own researchers consult with scientists around the country on a common issue, the research community, and public, gain a richer, more complete understanding of how we hear--and in less time."

Studying family members from Pakistan and southern India with a history of deafness, researchers at the NIDCD Laboratory of Molecular Genetics, together with scientists from universities in the United States, Pakistan, and southern India, pinpointed five different mutations that occur in the TMIE gene that result in non-syndromic hearing loss. The mutations caused incorrect amino acids to replace correct ones, key protein-encoding portions of the DNA molecule to be skipped over entirely, and the protein to be prematurely cut off. The protein that is normally encoded by the TMIE gene contains 156 amino acids and is like no other currently documented.

The study appears in the September 2002 issue of the American Journal of Human Genetics (published electronically July 24, 2002). Scientists who collaborated on the study are from the University of Iowa, Iowa City, Iowa; the University of Michigan Medical School, Ann Arbor, Michigan; the University of Madras, Madras, India; the Rotary Deaf School, Ichalkaranji, India; and the Center of Excellence in Molecular Biology, Lahore, Pakistan.

In the spinner mouse study, Dr. David Kohrman, assistant professor of otolaryngology and human genetics at the University of Michigan Medical School, Ann Arbor, Michigan, and scientists at The Jackson Laboratory, Bar Harbor, Maine, have discovered two mutations of the Tmie gene that result in profound hearing loss: a deletion of the entire gene and a base pair substitution that cuts the protein off before it completes its 153-amino-acid chain.

Mice that contain the Tmie mutations possess slowed, stunted, or otherwise abnormal sensory cells, called hair cells, in the inner ear, the team found, which suggests that the Tmie gene contributes to their normal development and maintenance. Hair cells, named for tiny hairlike extensions jutting upward from the cells in bundles, convert sound vibrations originating from the ear drum into nervous impulses that are interpreted by the brain. Because the missing end of the altered protein is similar in structure to that found in certain cell membranes, the gene may play a role in regulating interactions between the hair cell and its environment. This study appears in the September 1, 2002, issue of Human Molecular Genetics.

As the nation's focal point for research in human communication, the NIDCD supports and conducts research and research training on normal mechanisms as well as diseases and disorders of hearing, balance, smell, taste, voice, speech, and language that affect millions of Americans.

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