(Press-News.org) CINCINNATI – Researchers identify an underlying molecular process that causes a genetic form of non-syndromic deafness in a new study that also suggests affected families may be at risk of damage to other organs.
A multi-national research team led by scientists at Cincinnati Children's Hospital Medical Center report their findings in a study posted online Aug. 27 by the Journal of Clinical Investigation. The research opens the door to finding possible treatments for the condition (called DFNB49 non-syndromic hearing loss) and points to possible cellular damage in other organs like the heart, thyroid and salivary glands.
"Understanding the function of a deafness-causing mutation and the mechanism of disease progression is an important first step towards finding a therapeutic solution," said Saima Riazuddin, PhD, senior investigator and a scientist in the Division of Otolaryngology/Head and Neck Surgery at Cincinnati Children's. "But our study on mice also suggests we should clinically evaluate affected individuals more thoroughly, as they may have some other and not very obvious clinical problems involving multiple organs."
DFNB49 non-syndromic deafness is an inherited condition caused by mutations in the gene TRIC. Its "non-syndromic" designation means the hearing loss has not previously been linked to any other medical conditions.
To conduct their study, the researchers developed a first-ever "knock-in" mouse model of DFNB49 deafness by inserting mutations in the corresponding mouse version of the TRIC gene, known as Tric. This led to the loss of a critical protein called tricellulin in the mice.
Researchers report that loss of tricellulin disrupted the structure of what are called tight junctions in the epithelial cells of the cochlea in the inner ear. The authors suggest this affected the permeability of inner ear epithelia tissue, creating a possible channel that caused an imbalance in the quantity of ions and macromolecules. Researchers theorize this resulted in a detrimental environment and loss of cochlear hair cells, leading to hearing loss in the mice.
But the researchers also observed other unexpected characteristics in their newly generated Tric-mutated mice – potentially harmful alterations in the cellular structures of salivary glands, thyroid glands and in heart cells. The animals also had enlarged hearts, livers, spleens and kidneys.
In particular, the scientists pointed to enlarged nuclei in the cardiomyocyte cells of mice, suggesting the possibility that the gene mutation in mice is linked to myocardial hypertrophy in the animals – a dangerous thickening of the heart muscle.
The researchers stressed the need for additional research into their findings but cautioned against the immediate interpretation of data involving mouse models for treatment of human patients. Still, they suggest consideration of their findings is advisable in clinical follow-up of people with DFNB49.
"In previous studies, affected members of DFNB49 families did not reveal any other obvious conditions besides hearing loss, but the human families were not assessed to the same extent as the evaluation we conducted on the tricellulin mutant mice," said Riazuddin. "In light of our current findings, we are beginning to understand the broader function of tricellulin, and this study will guide us for further follow-up clinical evaluations of affected families to help us understand their complete medical spectrum."
###
Gowri Nayak, PhD, a research fellow at Cincinnati Children's (Pediatric Otolaryngology), led the study as a first author, under the guidance of Riazuddin (also an assistant professor of Pediatrics at the University of Cincinnati College of Medicine). Other collaborators included researchers from the National Institute on Deafness and other Communication Disorders, the National Heart, Lung and Blood Institute, the University of Kentucky (Department of Physiology), the University of Punjab in Lahore, Pakistan (National Center of Excellence in Microbiology), the University of Nebraska (Department of Special Education and Hearing Disorders) and University College of London in the United Kingdom (Centre for Auditory Research).
Funding support for the research came from the Deafness Research Foundation, Action on Hearing Loss, the National Institute on Deafness and other Communication Disorders (R01DC011748, DC011803, R01DC006443, R01DC009434, DC000039-15) and the International Center for Genetic Engineering and Biotechnology in Italy.
About Cincinnati Children's:
Cincinnati Children's Hospital Medical Center ranks third in the nation among all Honor Roll hospitals in U.S. News and World Report's 2013 Best Children's Hospitals ranking. It is ranked #1 for cancer and in the top 10 for nine of 10 pediatric specialties. Cincinnati Children's, a non-profit organization, is one of the top two recipients of pediatric research grants from the National Institutes of Health, and a research and teaching affiliate of the University of Cincinnati College of Medicine. The medical center is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally recognized research, education and innovation. Additional information can be found at http://www.cincinnatichildrens.org. Connect on the Cincinnati Children's blog, via Facebook and on Twitter.
Study identifies molecular process behind form of non-syndromic deafness
2013-08-27
ELSE PRESS RELEASES FROM THIS DATE:
Personalized AF management needed to close mortality gap
2013-08-27
Amsterdam, The Netherlands – Tuesday 27 August 2013: Personalised management is the only way to close the mortality gap for patients with atrial fibrillation (AF), according to an ESC consensus paper presented at ESC Congress 2013 by Professor Paulus Kirchhof (UK).
The Atrial Fibrillation competence NETwork (AFNET) and European Heart Rhythm Association (EHRA) consensus paper is published online in the European Journal of Pacing, Arrhythmias, and Cardiac Electrophysiology (EP-Europace)1 and presented during the ESC Congress session on personalised cardiology.
Professor ...
A genetic treasure hunting in sorghum may benefit crop improvement
2013-08-27
August 27, 2013, Shenzhen, China - A consortium of researchers from The University of Queensland, the Queensland Department of Agriculture, Fisheries and Forestry (DAFF Qld) and BGI has discovered that sorghum, a drought-tolerant African crop, holds vastly more genetic variation than previously reported. This study published in Nature Communications today provides an invaluable resource for the genetic improvement of sorghum and other grass species.
Sorghum is not only a food and feed cereal crop, but also can be used as the basis of biofuel. Its resistance to heat and ...
Novel approach to gene regulation can activate multiple genes simultaneously
2013-08-27
CAMBRIDGE, Mass. (August 27, 2013) – By creating a powerful new gene regulation system called CRISPR-on, Whitehead Institute researchers now have the ability to increase the expression of multiple genes simultaneously and precisely manipulate each gene's expression level. The system is effective in both mouse and human cells as well as in mouse embryos.
"CRISPR-on is a tool that will be very useful for studying many biological processes, particularly for studying gene functions and gene networks," says Whitehead Founding Member Rudolf Jaenisch. "In contrast to RNA interference, ...
European hunter-gatherers owned pigs as early as 4600BC
2013-08-27
European hunter-gatherers acquired domesticated pigs from nearby farmers as early as 4600BC, according to new evidence.
The international team of scientists, including researchers at Durham and Aberdeen universities, showed there was interaction between the hunter-gatherer and farming communities and a 'sharing' of animals and knowledge. The interaction between the two groups eventually led to the hunter-gatherers incorporating farming and breeding of livestock into their culture, say the scientists.
The research, published in Nature Communications today (27 August), ...
Long-term memory in the cortex
2013-08-27
'Where' and 'how' memories are encoded in a nervous system is one of the most challenging questions in biological research. The formation and recall of associative memories is essential for an independent life. The hippocampus has long been considered a centre in the brain for the long-term storage of spatial associations. Now, Mazahir T. Hasan at the Max Planck Institute for Medical Research and José Maria Delgado-Garcìa at the University Pablo de Olavide of Seville, Spain, were able to provide first experimental evidence that a specific form of memory associations is ...
Earthquakes and tectonics in Pamir Tien Shan
2013-08-27
Earthquake damage to buildings is mainly due to the existing shear waves which transfer their energy during an earthquake to the houses. These shear waves are significantly influenced by the underground and the topography of the surrounding area. Detailed knowledge of the landform and the near-surface underground structure is, therefore, an important prerequisite for a local seismic hazard assessment and for the evaluation of the ground-effect, which can strongly modify and increase local ground motion.
As described in the latest issue of Geophysical Journal International, ...
Computer test reveals high prevalence of attention disorders in stroke patients
2013-08-27
A majority of stroke patients have problems paying attention and could be helped by brain-training computer games, a new study suggests.
Researchers at Imperial College London found that problems such as difficulty filtering out distractions, difficulty following instructions, and reduced alertness are much more common in stroke patients than doctors realise.
Their study, published in Neurology, showed that brain scans and bedside tests can be used to diagnose these three types of attention problems, each of which could be addressed with computer games tailored for the ...
Existence of new element confirmed
2013-08-27
An international team of researchers, led by physicists from Lund University, have confirmed the existence of what is considered a new element with atomic number 115. The experiment was conducted at the GSI research facility in Germany. The results confirm earlier measurements performed by research groups in Russia.
"This was a very successful experiment and is one of the most important in the field in recent years", said Dirk Rudolph, Professor at the Division of Atomic Physics at Lund University.
Besides the observations of the new chemical element, the researchers ...
New energy model offers transparency to let others replicate findings
2013-08-27
Computer models are used to inform policy decisions about energy, but existing models are generally "black boxes" that don't show how they work, making it impossible for anyone to replicate their findings. Researchers from North Carolina State University have developed a new open-source model and are sharing the data they put into it, to allow anyone to check their work – an important advance given the environmental and economic impact of energy policy decisions.
"Most models show you the math behind how they work, but don't share the source code that is supposed to implement ...
An alga stressed by the light
2013-08-27
This news release is available in Spanish.
Gelidium corneum is a very common alga along the Basque coast. It grows at a depth of between 3 and 15 metres, and from September onwards can be seen out of the water. It gets broken up by storms and washed up on the beaches where it forms a red carpet. On some parts of the coast, above all in transparent water zones, the fronds of the algae have turned yellowish. The researchers have identified this change as a symptom of stress.
There are more sunny days during the summer which is when the algae are exposed to increased ...