Researchers have recently linked hearing loss to a specific DNA deletion, using whole-genome sequencing.
Jeanne and Andy Nadeau agreed to participate in the study back in 2011. Five of the parents’ 10 children suffer from hearing loss and the Nadeaus wanted to understand the cause of their children’s hearing damage.
Although the Nadeaus’ previous genetic tests had inconclusive results, they agreed to participate in the researchers’ study, which would more broadly examine their family’s genes.
“If they called and said, ‘Hey, we found out something bad is coming in the next five to 10 years,’ that’d be devastating, but I’d take advantage of knowing it,” Jeanne told The Boston Globe.
Whole Genome Sequencing
Whole-genome sequencing examines each of the 3 billion letters of DNA to determine the genetic risk factors for disease. Originally a tool used primarily in research, this technology is now a medical test a rising number of hospitals and testing companies are offering to patients for a myriad of purposes, from hunting down the cause of a mysterious illness to identifying effective treatments to searching for disease risk factors.
Partners HealthCare’s Laboratory for Molecular Medicine analyzed the Nadeau’s DNA. This summer, the lab became one of the first health care systems to offer genome sequencing and analysis for 9,000 dollars.
Planning for the Future
Partners Healthcare’s test discovered a specific DNA deletion that caused the Nadeau children’s symptoms. Although the Nadeaus’ experience was a scientific success, whole-genome testing is still so new that researchers are uncertain about which cases will be covered by insurance.
Maria, Noah, Laura, Lucia and Alyssa Nadeau’s hearing loss has certainly shaped the family and fostered closeness among the siblings, who range in age from 1 to 20. The All of the Nadeaus, including those with hearing damage, perform as a family band at churches, retreats and open mike nights.
The Nadeau children experience neither complete deafness nor normal hearing loss. Instead, they have a type of hearing loss called a “cookie bite,” because their hearing frequencies, when plotted on a graph, look like someone took a bite out of the middle.
Searching for Answers
Although genetic testing, which looked for mutations known to cause hearing loss in the children, failed to find anything, it did introduce them to the Partners Laboratory for Molecular Medicine.
The laboratory’s chief director Heidi Rehm suspected that a recessive genetic disorder caused the hearing loss. Every person carries two copies of a gene and Rehm speculated that Jeanne and Andy, neither of whom experienced hearing damage, each likely carried one mutated recessive copy of a hearing-related gene and one normal dominant one. Their children would have a one in four chance of inheriting two mutated copies, which leads to hearing loss.
The Partners genetics team sequenced the genomes of three Nadeau children. When the lab’s first attempt to analyze the data proved unsuccessful, they put the case aside until Jeanne mentioned that Andy’s father had experienced hearing loss at an early age. When the team reanalyzed the children’s DNA, they found 31 genetic changes in hearing loss-related genes but were unsure which genetic change was the cause of the problem.
“The real challenge is when do you stop looking?” Rehm told The Boston Globe.
Researchers ultimately used a different kind of analysis to find a noticeable gap – a genetic deletion that covered four genes. The Nadeau children with hearing damage held two copies of the genetic deletions.
Using this new information, the researchers created a test for genetic causes of hearing loss with the hope of identifying more affected families and studying a potential connection to vision problems. Jeanne clamed that the children suffering from hearing loss also experienced headaches, a sign they needed glasses.
Dr. Bruce Korf, chairman of the University of Alabama at Birmingham’s department of genetics, told The Boston Globe that there are limits to how useful sequencing can be in the doctor’s office, since the human genome is largely unexplored.
Jeanne Nadeau has discussed the genetic test results with her three oldest children. Maria is glad she understands the genetic cause of her hearing loss.
“I am happy to know it,” Maria told The Boston Globe. “Knowing it doesn’t make it go away.”