Nav: Home

Researchers find novel mutation affecting YARS causes multisystem disease

November 06, 2018

STRASBURG, PA- Researchers have identified a novel missense mutation in tyrosyl-tRNA synthetase (YARS c.499C>A, p.Pro167Thr) that causes a severe recessive disorder in affected individuals. The study, led by clinicians, researchers and collaborators of the Clinic for Special Children in Strasburg, PA, appears in Human Molecular Genetics. The report includes detailed clinical characterization of seven related Amish children who were homozygous for the variant. The children all exhibited poor growth, developmental delay, abnormal brain white matter, hearing loss, involuntary eye movements, progressive cholestatic liver disease, pancreatic insufficiency, hypoglycemia, anemia, intermittent excess of protein in urine, recurrent bloodstream infections, and chronic pulmonary disease.

YARS directs the production of the aminoacyl-tRNA synthase protein, which catalyzes the attachment of the amino acid tyrosine to its corresponding tRNA as an essential step in the translation of the genetic code to protein. Functional assays in yeast demonstrated that the YARS p.Pro167Thr substitution causes reduced protein function and poor cell growth. Protein-protein interaction studies in human embryonic kidney cells also show that this change results in the reduced homodimerization process, which is essential for the protein's catalytic function. In contrast to previous reports of other variants in YARS, related adults heterozygous for the c.499C>A variant showed no evidence of damage to peripheral nerves on electromyography.

The children in the study share some of the same phenotypic features as children in previous reports, but also broaden the phenotypic spectrum to include auditory, hematologic and renal symptoms. This report is the first in the broader category of ARS-opathies that includes pancreatic dysfunction. A deeper understanding of YARS in human disease may inspire innovative therapies and improve the care of affected patients.
-end-


Clinic for Special Children

Related Hearing Loss Articles:

Researchers listen to zebrafish to understand human hearing loss
Can a fish with a malformed jaw tell us something about hearing loss in mice and humans?
Postmenopausal hormone therapy associated with higher risk of hearing loss
Use of postmenopausal hormone therapy was associated with higher risk of hearing loss, and the risk tended to increase with longer duration of use.
Few researchers consider hearing loss in healthcare communication: Study
Of the 67 papers reviewed, only 16 (23.9 percent) included any mention of hearing loss.
Few studies consider hearing loss when assessing communication with physicians
Doctors believe that communication with those under their care is important, but most studies of communication between physicians and older adults do not mention that hearing loss may affect this interaction.
Study shows hearing tests miss common form of hearing loss
Traditional clinical hearing tests often fail to diagnose patients with a common form of inner ear damage that might otherwise be detected by more challenging behavioral tests, according to the findings of a University at Buffalo-led study published in the journal Frontiers in Neuroscience.
More Hearing Loss News and Hearing Loss Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Teaching For Better Humans
More than test scores or good grades — what do kids need to prepare them for the future? This hour, guest host Manoush Zomorodi and TED speakers explore how to help children grow into better humans, in and out of the classroom. Guests include educators Olympia Della Flora and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#535 Superior
Apologies for the delay getting this week's episode out! A technical glitch slowed us down, but all is once again well. This week, we look at the often troubling intertwining of science and race: its long history, its ability to persist even during periods of disrepute, and the current forms it takes as it resurfaces, leveraging the internet and nationalism to buoy itself. We speak with Angela Saini, independent journalist and author of the new book "Superior: The Return of Race Science", about where race science went and how it's coming back.