Genetic hearing screening for newborns

DESCRIPTION (provided by applicant): Most states in the United States mandate a universal newborn hearing screening (UNHS) and average coverage rate is ~93% among newborns. However, most of those (gt90%) who failed UNHS are false positives. More importantly, current methods for UNHS are unable to detect early-onset hearing loss and provide a diagnosis that defines underlying etiology among those real positives. More than half of congenital hearing loss cases in developed countries are caused by genetic mutations. Currently 46 deafness genes are identified with a combined total mRNA length of about 203k base pairs. Concurrent diagnostic analysis of all these genes is considered impossible until the commercialization of DNA sequencing systems that can analyze millions of short DNA fragments in a massively-parallel fashion. However, widespread applications of the new technology are hindered by the high per-patient cost needed to carry out front-end preparations to capture targeted deafness genes from the human genome. This STTR project will test and validate the core technology for a low-cost approach to efficiently capture exons of deafness genes and its suitability for coupling with the massively-parallel sequencing system for the detection of genetic mutations. We will test a device based on biotinylated cDNA bait probes fixed on streptavidin- coated magnetic microspheres, which can be manufactured in-house without the use of any specialized equipment. The ultimate goal of the project is to provide a cost-realistic implementation protocol for a DNA-based hearing screening method that will significantly enhance the current UNHS program. PUBLIC HEALTH RELEVANCE: Hearing impairments affect about 30 million Americans, which has enormous public health and social-economical impacts. Universal newborn hearing screening (UNHS) is mandated by law in almost all the states in the United States. In developed countries, most congenital deafness cases are caused by genetic mutations. Therefore, efficient and accurate genetic analysis technology for newborns who are screened positive by physiology-based methods is a key requirement for further treatment, clinical counseling and disease management. Deafness genes are extremely heterogeneous. So far 46 deafness genes with a combined mRNA length of 203k base pairs are confirmed. Current routine clinical services, however, only analyze 2-3 small genes. Concurrent diagnostic analysis of all these genes is considered impossible until the commercialization of DNA sequencing systems that can analyze millions of short DNA fragments in a massively-parallel fashion. However, one major obstacle for a widespread application of the new technology is the high per-patient cost needed to carry out front-end preparations to capture targeted deafness genes from the human genome. This STTR project will test and validate the core technology for a low-cost approach to efficiently capture exons of deafness genes and its suitability for coupling with the massively-parallel sequencing system for the detection of genetic mutations. The ultimate goal of the STTR project is to provide a cost-realistic implementation protocol for a DNA-based hearing screening method that will significantly enhance the current UNHS program.