SEQaBOO (SEQuencing a Baby for an Optimal Outcome) will translate high-throughput genomic approaches into routine newborn screening for hearing loss (HL). The project will enroll approximately 500 newborns that do not pass their initial newborn hearing screen and their parents for genomic sequence analysis. Until recently, clinical diagnosis of congenital defects without an overt anatomical malformation, such as hearing loss, was profoundly limited. Today, congenital HL and other subtle birth defects are recognized in newborns, allowing early interventions that limit life-long disabilities. Development of next generation DNA sequencing technologies provides a new opportunity for researchers and clinicians dedicated to improving the lives of newborns with birth defects to investigate whether genetic etiologies of congenital defects can be more accurately and efficiently defined and whether improved genetic diagnosis translates into superior clinical care. In this project we aim to address this challenge by assessing the clinical impact of genomic data in newborns with congenital HL. For newborns in whom no pathogenic mutation is identified via exome sequencing, alternative genomic approaches will be used to explore comprehensively the full mutational spectrum across the genome. Analytic pipelines will be developed to provide automated and accurate clinical interpretation of genomic variants. When appropriate, genetic information will be returned to parents and physicians for early intervention purposes. Although diagnosed in the early neonatal period and not life threatening, HL requires a number of adjustments by the family and patient to optimize quality of life. In some instances, cochlear implants can restore hearing to near normal levels. Other therapeutic interventions for congenital HL are under development. As there are a remarkable number of different etiologies of congenital HL that range from genetic mutation to viral infection, we surmise that appropriate therapies may vary depending on precise etiology. Genetic causes of HL are highly heterogeneous and mutations in >115 genes have already been identified. In this proposal, we will test the hypothesis that rapid discovery of the exact cause of a newborn's HL will benefit management and therapeutic interventions. Annually we will survey the cohort of children to ascertain general health, including speech and language development in addition to hearing status, and parental attitudes on genomic sequencing. In sum, we will analyze and assemble genomic datasets, perform clinical genomic research of HL identifiable through newborn screening and explore implications of integration of genomic sequencing into newborn screening. All of this will inform the impact of genomic sequencing on the care and management of newborns with congenital HL and allow us to investigate factors associated with our society's acceptance of this new technology for optimal outcome of a newborn baby.

Public Health Relevance

More than 4 million infants undergo newborn screening every year, including testing for hearing loss. These tests aim to identify babies with birth defects and other abnormal conditions so that doctors can appropriately treat these babies. The SEQaBOO project proposes to use the latest DNA sequencing and genetic technologies to define better the genetic causes of hearing loss, with an overarching goal of offering better and timelier treatment options for babies born with hearing loss.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC015052-03
Application #
9441752
Study Section
Special Emphasis Panel (ZDC1)
Program Officer
Watson, Bracie
Project Start
2016-03-01
Project End
2021-02-28
Budget Start
2018-03-01
Budget End
2019-02-28
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115