2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Exome Sequencing Analysis Reveals Enrichment of Variants in Known Autosomal Dominant Hearing Loss Genes in Patients With Presbycusis

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A study conducted by the Mayo Clinic found that variants in specific genes may play a role in age-related hearing loss, also known as presbycusis. The study analyzed genetic data from 100 patients with presbycusis and identified variants in several autosomal dominant genes that were enriched in this group. The findings suggest that these specific genes may be more actively involved in presbycusis and could be potential targets for genetic testing. The study also suggests that genetic testing in older patients should be done more frequently than current recommendations.<br /><br />The study population consisted of 100 cases, with 51 of them being male. The average age of the patients was 75.7 years. By analyzing the genomic data, the researchers identified 115 variants of interest (VOI) in six genes that were most commonly associated with presbycusis. These genes included TECTA, COL2A1, DIAPH1, DNMT1, NLRP3, and MYH9.<br /><br />Further analysis revealed that some of these genes had variants located in specific domains or regions. For example, NLRP3 had variants in the Leucine Rich Repeats Ribonuclease Inhibitor domain, which is associated with pathogenicity. TECTA had the most missense variants, and they were all predicted to be likely pathogenic. COL2A1 variants also had high pathogenicity scores. DIAPH1 variants were found in different regions of the gene. MYH9 had a variant that was highly suggestive of being pathogenic.<br /><br />The study excluded variants in recessive hearing loss genes and variants in DSPP that were located in a repetitive region. The researchers compared their results to a control group from the Tapestry study without hearing loss to further validate their findings.<br /><br />In conclusion, this study highlights the potential role of specific genes in presbycusis and suggests that genetic testing in older patients should be considered. Further research and analysis of these genomic regions could provide a better understanding of the genetic factors contributing to age-related hearing loss.

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Presenting Author - Stefan L. Farrugia, BS; Co-Author - Rory Olson, PhD; Co-Author - Eric Klee; Co-Author - Lisa A. Schimmenti, MD, FAAP, FACMG;

Meta Tag

Bioinformatics

Clinical History

Databases

Etiology

Exome sequencing

Genome sequencing

Genomic Methodologies

Identification of Disease Genes

Susceptibility Locus

Co-Author Rory Olson, PhD

Co-Author Eric Klee

Co-Author Lisa A. Schimmenti, MD, FAAP, FACMG

Presenting Author Stefan L. Farrugia, BS

Keywords

Mayo Clinic

age-related hearing loss

presbycusis

genetic variants

autosomal dominant genes

genetic testing

older patients

genomic data

variants of interest

specific genes