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

Utility of Genetic Testing in Detection of Late-Onset Hearing Loss

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.

Study Overview

• Status: Completed
• Conditions: Hearing Loss; Deafness; Late-Onset Hearing Loss
• Intervention / Treatment: Genetic: No intervention

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 3681

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Topeka, Kansas, United States, 66604
      • Stormont-Vail HealthCare
  • Ohio
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Integris Baptist Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 weeks (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Hospital

Description

Inclusion Criteria:

• Documentation of informed consent
• Inborn
• Ability to do ABR (auditory brainstem response screen technology) screening test on all participants
• Age at enrollment less than 14 days or less than or equal to 336 hours (Birth date is day 0)
• Gestational age > = 34 0/7 weeks and above. (Late preterm infants and term infants)
• No major anomalies
• Ability to obtain blood sample prior to administration of any blood product transfusion
• Subjects' parents or legal guardian willing to provide follow-up data on their child. They will need to provide a telephone contact number and address for follow-up procedures

Exclusion Criteria:

• Older than 14 days of age or 336 hours
• Receipt of a blood product prior to the ability to obtain blood sample for genetic testing (SoundGene panel)
• Any major congenital anomalies. (chromosomal abnormalities, cyanotic congenital heart disease, gastroschisis, omphalocele, diaphragmatic hernia, or other major gastrointestinal anomalies, major neurological injury or anomaly, and multiple congenital anomalies)

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: Pediatrix
• Investigators: Principal Investigator: Gail Lim, ARNP, Pediatrix; Study Chair: Zhili Lin, MD, PhD, Pediatrix Screening; Study Chair: Reese H Clark, MD, Pediatrix

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: August 2, 2007
• First Submitted That Met QC Criteria: August 2, 2007
• First Posted (Estimate): August 3, 2007

Study Record Updates

• Last Update Posted (Estimate): March 1, 2012
• Last Update Submitted That Met QC Criteria: February 28, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: Hearing Loss; Deafness; Late-Onset Hearing Loss
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Hearing Loss; Deafness
• Other Study ID Numbers: PDX-001-07