Adult-onset hearing loss breakthrough as common inherited genetic variant found

Research led by experts at the Radboud University Medical Center in the city of Nijmegen, Holland, found that the "RIPOR2 variant is estimated to be present in more than 13 000 individuals who are therefore at risk of developing HL or have developed HL already due to this variant". The study, published in the BMJ Journal of Medical Genetics, indicates that inheriting this variant puts about 30 000 additional individuals at risk in northwest Europe.

Despite high heritability being known to be behind adult-onset deafness—an estimated 30% to 70%—the causes have long remained a mystery, even though 118 genes have been identified to help explain early onset (child or congenital cases) hearing loss. While previous work by the researchers had already discovered the chromosomal region involved in hearing loss in one family, the actual gene affected by the deletion had remained elusive.

The breakthrough was made using family and cohort studies including exome sequencing and characterisation of the hearing phenotype. In 39 of 40 family members with confirmed hearing loss, the identical RIPOR2 genetic variant was found. It was also discovered in two people aged 49 and 50 who weren't affected by hearing loss, and in a further 18 out of 22,952 randomly selected people for whom no information on hearing loss was available.

The authors underline in their conclusions that "we have demonstrated that an adult-onset type of HL (DFNA21) is relatively common and associated with a ‘mild’ variant in RIPOR2. Potentially thousands of individuals in the Netherlands and beyond are at risk of developing HL."

"Further such variants might well wait to be ‘unmasked’ as (population-specific) frequent and highly penetrant causes of adult-onset HL," the paper goes on. "Because of the large number of subjects estimated to be at risk for HL due to the […] RIPOR2 variant, it is an attractive target for the development of a genetic therapy. The great progress that is being made in hearing disorders is promising."

Source: Journal of Medical Genetics