The Natural History of TMPRSS3-related Hearing Loss
Article Summary
- Dr. Xue Zhong Liu led an international study to define the natural history of TMPRSS3-related hearing loss.
- Hearing loss affects more than 1.5 billion people and genetic mutations like TMPRSS3 mutations cause more than half of those.
- Dr. Liu believes the work is a critical step in translating hearing loss research to clinical studies and, eventually, therapies.
According to the World Health Organization, hearing loss affects 1.5 billion people worldwide. More than 400 million people live with disabling hearing loss.
More than half of those cases stem from genetics. TMPRSS3, for example, is a hereditary disease caused by mutations of the TMPRSS3 gene. Resulting hearing loss can be mild to profound and is generally progressive. The prevalence of TMPRSS3 mutations makes it an excellent potential target for gene therapy.
Tracing the History of TMPRSS3
After successfully restoring hearing in a TMPRSS3 mouse model mimicking genetic hearing loss in humans, Xue Zhong Liu, M.D., Ph.D., professor of otolarygology and human genetics and director of the Miami Ontogenetic Program, and team initiated an international, multicenter study to define the natural history of TMPRSS3-related hearing loss for human gene therapy trials.
Dr. Liu lead an international consortium to gather a massive trove of data about clinical genetic testing, serial audiograms, age at hearing loss diagnosis, hearing-assistive device status, speech perception testing after cochlear implantation, and hearing loss progression over time from more than 150 participants recruited from 16 centers in six countries.
The team analyzed the genetic and clinical features of the participants to explore the genotype-to-phenotype correlations of TMPRSS3 variants, specifically audiological patterns, hearing loss progression over time, cochlear implant outcomes and predictive protein structure modeling of TMPRSS3 variants for use in future experimentation.
The Genetics of TMPRSS3 Hearing Loss
The study results, published in Human Genetics, provide new insights into the genetic basis of TMPRSS3-related hearing loss and will impact genetic counseling and the timing of targeted therapies.
“In humans with some TMPRSS3 mutations, hearing loss does not manifest until adulthood,” said Dr. Liu, the Marian and Walter Hotchkiss Endowed Chair in Otolaryngology at the Miller School. “Accurate, natural history with genotype-phenotype correlations will aid TMPRSS3-related hearing loss patient care and continued therapeutic development.”
The study was also the largest examination of TMPRSS3 genotype-phenotype correlations and suggests treating TMPRSS3-related hearing loss even at an advanced age is feasible.
“These findings provide insight for genetic counseling and the ongoing design of novel gene therapeutic approaches.” Dr. Liu said.
He added that the study is a crucial step in translating scientific discoveries into first-in-human clinical trials and, ultimately, life-changing treatments for patients.
Tags: Dr. Xue Zhong Liu, genetic variants, hearing loss, otolaryngology