TAU geneticist discovers mutation causing deafness

The discovery could help affected families undergo genetic counseling to avoid such a defect in future children.

DNA strand double helix 311 (photo credit: Jerome Walker)
DNA strand double helix 311
(photo credit: Jerome Walker)
New Israeli research led by a Tel Aviv University geneticist has identified six critical gene mutations in Israeli Jewish and Palestinian families, one of which was found to have been involved in genetic hearing loss of 34 percent of Jews of Moroccan origin.
The discovery, published Wednesday in BioMed Central’s open-access journal Genome Biology, could help affected families undergo genetic counseling to avoid such a defect in future children.
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Prof. Karen Avraham of the Sackler Medical School explained that most cases of early-onset hearing loss are genetic in origin, but there are many different forms, almost a third of which are associated with other clinical problems.
Thus, she said, it can be difficult to pinpoint the exact genes responsible as mutations vary between countries and populations.
But her team, which included doctors and scientists both in Israel and at Bethlehem University of the Palestinian Authority, used “targeted genomic capture and massively-parallel sequencing to identify genes for hereditary hearing loss in Middle Eastern families.”
They screened a total of 246 genes in 11 unrelated individuals known to be responsible for human or mouse deafness.
All of the individuals were believed to have hereditary deafness.
Once a mutation was found, it was tested in an extended pool of families with hearing loss and compared to data for people with normal hearing.
One mutation was found in 34% of the Moroccan Jewish population but not in any other Israeli Jews, while another was discovered in a Palestinian Arab family.
Avraham noted that “the two-tier method we used allowed us to scan exons of genes, thought to be involved in hereditary deafness, and their flanking sequences. This meant that we were able to quickly target specific genes and find multiple mutations responsible for hearing loss.
Use of genomic analysis in early clinical diagnosis of hearing loss will enable prediction of related phenotypes and show us where to look to find the biological mechanisms involved in hearing loss.”
She noted that ordinary gene sequencing is expensive and time-consuming, but exome sequencing – focusing on exons, which are short, functionally important DNA sequences that represent regions in genes translated into protein and the untranslated regions flanking them – is much more rapid and cheaper to perform.
When only the individual’s exons are sequenced, by first capturing the DNA with relevant probes, researchers can zoom in on specific sites, reducing the amount of code they need to cover, to find mutations that cause disease.
Avraham, of TAU Sackler Medical Faculty’s department of human molecular genetics and biochemistry, said that her team has “had the DNA in our freezer for 12 years, unable to find a result, but in one month using the new technique, we were able to solve many family cases.”
“Each family that comes to a clinic cares very much why they are deaf, and for many of them, we can provide an answer in a much more reasonable amount of time.” She noted that the Palestinian mutation was rare, and only one was found.
“We are discussing why we found fewer mutations in this group, but the relevance of finding mutations is for both populations.”