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The SLC26A4 c.706C>G (p.Leu236Val) Variant is a Frequent Cause of Hearing Impairment in Filipino Cochlear Implantees

Chiong, Charlotte M.*,†,§; Reyes-Quintos, Ma. Rina T.*,†,‡,§; Yarza, Talitha Karisse L.*,†; Tobias-Grasso, Celina Ann M.; Acharya, Anushree#; Leal, Suzanne M.#; Mohlke, Karen L.**; Mayol, Nanette L.††,‡‡; Cutiongco-de la Paz, Eva Maria‡,||; Santos-Cortez, Regie Lyn P.§§

doi: 10.1097/MAO.0000000000001893
BASIC SCIENCE
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Hypothesis: Variants in SLC26A4 are an important cause of congenital hearing impairment in the Philippines.

Background: Cochlear implantation is a standard rehabilitation option for congenital hearing impairment worldwide, but places a huge cost burden in lower-income countries. The study of risk factors such as genetic variants that may help determine genetic etiology of hearing loss and also predict cochlear implant outcomes is therefore beneficial.

Methods: DNA samples from 29 GJB2-negative Filipino cochlear implantees were Sanger-sequenced for the coding exons of SLC26A4. Exome sequencing was performed to confirm results.

Results: Four cochlear implantees with bilaterally enlarged vestibular aqueducts (EVA) were homozygous for the pathogenic SLC26A4 c.706C>G (p.Leu236Val) variant, which has a minor allele frequency of 0.0015 in Filipino controls. In patients with the SLC26A4 variant there was no association between cochlear implant outcome and age at implantation or duration of implant. There was also no association between the occurrence of the SLC26A4 variant and postsurgical audiometric thresholds and parents’ evaluation of aural/oral performance of children (PEACH) scores. On the other hand, the SLC26A4 variant increased presurgical median audiometric thresholds (p = 0.01), particularly at 500 to 2000 Hz.

Conclusion: The SLC26A4 c.706C>G (p.Leu236Val) variant is a frequent cause of congenital hearing impairment in Filipinos and is associated with bilateral EVA and increased presurgical audiometric thresholds, but does not adversely affect post-implant outcomes.

*Philippine National Ear Institute

Newborn Hearing Screening Reference Center

University of the Philippines Manila-National Institutes of Health

§Department of Otorhinolaryngology

||Department of Pediatrics, University of the Philippines Manila-Philippine General Hospital, Manila

MED-EL, Innsbruck, Austria

#Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas

**Department of Genetics, University of North Carolina, Chapel Hill, North Carolina

††Office of Population Studies Foundation

‡‡Department of Anthropology, Sociology and History, University of San Carlos, Cebu, Philippines

§§Department of Otolaryngology, University of Colorado School of Medicine, Aurora, Colorado

Address correspondence and reprint requests to Charlotte M. Chiong, M.D., Ph.D., Ear Unit, 2nd Floor, Philippine General Hospital, Taft Ave., Manila, Philippines; E-mail: charlotte_chiong@yahoo.comcmchiong@up.edu.ph

Sources of Funding: This study was funded by grants from the Department of Science and Technology-Philippine Council for Health and Research Development and the University of the Philippines Manila-National Institutes of Health (to C.M.C.). Sanger sequencing of controls was funded by National Institutes of Health (NIH) - National Institute on Deafness and Other Communication Disorders grants R01 DC003594 and R01 DC011651 (to S.M.L.). The Cebu Longitudinal Health Survey (CLHNS) was supported by NIH grants DK078150, TW005596, HL085144, and TW008288 and pilot funds from RR020649, ES010126, and DK056350. They thank the Office of Population Studies Foundation research and data collection teams and the study participants who generously provided their time for the CLHNS study.

CAM Tobias is an employee of MED-EL. MED-EL did not have a role in the study design, data collection, analysis and interpretation, or manuscript writing and submission. All authors declare no conflict of interest.

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