Genetic Testing in Detection of Late-Onset Hearing Loss (SoundGene)

Two major limitations of existing audiometric newborn hearing screening programs are their inability to detect forms of deafness that are not expressed at birth and the low compliance with obtaining recommended audiologic confirmation and/or follow-up. Molecular genetic tests on blood spots from all newborns will identify those at risk for the most frequent causes of late-onset hearing loss and to add these infants to the group who should receive continued audiologic monitoring.

The specific aims of this project are to:

• Demonstrate the utility of detecting four potentially important causes of delayed onset hearing loss by molecular tests at birth, which may be missed by current audiometric screening tests.
• Document the frequency, clinical and genetic characteristics of hearing loss associated with each condition.

Dried blood spots (DBS) on filter paper will be obtained and be used for this project with parental informed consent from 6,000 newborn infants at approximately 25 hospitals. Pediatrix Screening, a subsidiary of Pediatrix Medical Group with long experience in high throughput neonatal testing, will perform genetic testing on the samples. The four genetic and environmental forms of deafness to be studied include:

• Prenatal/congenital cytomegalovirus (CMV) infection

  -Detecting the presence of CMV viral DNA in dried blood spots.

• Connexin Deafness - GJB2 and GJB6 mutations

  - Cx26 35delG, Cx26 235delC, Cx26 167delT, Cx26 M34T, and Cx30 large deletion.(Under sublicense with Athena Diagnostics, Inc: United States Patent Numbers: 5,998,147 and 6,485,908 and patents pending)

• Pendred Syndrome - SLC26A mutations

  - L236P, 1001 +1G>A, T416P, E384G

• Mitochondrial Mutations - T961C, T961G, G951A, 961 delT+C(n)Ins, G7444A, A7445G, A7445C.