Implementing Genomic Medicine in Care of Patients with Impaired Hearing

Abstract

Objectives:

The Miami Otogenetic Program has provided a unique platform to carry out translational research on delivering genetic services to deafness patient care. Using target-enrichment/NGS, we will 1) determine the overall frequencies of different forms of genetic deafness, 2) identify new genes for ARSNHL and ADNSHL, and 3) create a Genomic Deafness Database (GDD) and Personalized Sequence Profile (PSP) for the clinical care of deaf patients.

Methods:

We collected a unique cohort of multiplex families derived from three unique sources from the U.S., China, and Turkey, suitable for determination of molecular epidemiology of hereditary deafness and for new gene identification using “target-enrichment,” methods and next generation sequencing (NGS). Our interdisciplinary and collaborative team will conduct outcomes evaluation of genetic service on deaf patient care in our diverse populations.

Results:

The infrastructure of our multidisciplinary otogenetics team is presented along with our use of testing algorithms when evaluating patients with sensorineural hearing loss (SNHL). A total of 60% of small multiplex families are identified to have mutations in the known deafness genes in a pilot study and the remaining 40% have mutations in other yet-unidentified deafness-causing genes. We have identified several new genes for SNHL.

Conclusions:

The combined target-enrichment/NGS is a powerful tool in the identification of new deafness genes in small multiplex families and large multi-generational families. The multidisciplinary team approach is an effective way to bring the sequencing data to clinical practice for the clinical diagnosis and management of deaf and hard-of-hearing families.