DATE: May 9, 2017
TIME: 8:00am PT, 11:00am ET

Hearing loss is the most common sensory defect in humans. It affects 360 million people worldwide and by 2020, that number is predicted to reach 1 billion. The genetic and allelic heterogeneity associated with hereditary deafness are well established. Over 90 genes and 2000 mutations are causally linked to non-syndromic hearing loss (NSHL), which exhibits a wide spectrum of phenotypic diversity in onset, severity, progression and audioprofiles. Developing a comprehensive approach to tackle this extraordinary heterogeneity has become the cornerstone for genetic analysis. Capitalizing on technological advances, we have developed OtoSCOPE®, a next-generation sequencing platform that simultaneously screens 152 genes known to cause NSHL as well as common syndromic forms.

We sought to make this analysis widely available as an inexpensive and highly informative genetic analysis that would assist in the evaluation of persons with hearing impairment. To achieve this goal, we developed and optimized a customized pipeline to identify, annotate, categorize and prioritize sequence variants including SNVs, indels and importantly, copy number variations (CNVs). We also implemented a multidisciplinary approach that integrates a set of tools to determine the clinical significance of genetic variations. For example, we have created the Deafness Variation Database (DVD), an open-access database of all variants in all genes implicated in NSHL, and AudioGene, a machine-learning algorithm that analyzes audiometric data to predict likely genetic causes of deafness. AudioGene can also identify audiometric outliers at each deafness locus.

During this webinar, we will present the challenges we have faced and the solutions we have created to overcome them. We will discuss the knowledge we have acquired that has advanced our understanding of the molecular genetics of deafness. We will also showcase specific case studies to highlight the genetic and phenotypic complexities of hereditary deafness.

Learning objectives

• Targeted gene panels for deafness offer an efficient, cost-effective, customizable, high-throughput and high-depth sequencing approach to detect rare variants and CNVs, and to shed light on the hidden complexities of hereditary deafness
• The massive depth of coverage associated with targeted gene panels facilitates the detection of CNVs, which make a significant contribution to NSHL. Their detection must be integrated in all NGS pipelines for deafness.   
• Most identified deafness variants are novel or rare, and of unknown significance, making their interpretation challenging. The integration of audiometric and genetic data facilitates meeting this challenge.