Charlotte M. Chiong, Rina T.Ma. Reyes-Quintos, Talitha Karisse L. Yarza, Celina Ann M. Tobias-Grasso, Anushree Acharya, Suzanne M. Leal, Karen L. Mohlke, Nanette L. Mayol, Eva Maria Cutiongco-De La Paz, Regie Lyn P. Santos-Cortez
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. © 2018 Lippincott Williams and Wilkins. All rights reserved.
Philippine National Ear Institute, University of the Philippines Manila-Philippine General Hospital, Manila, Philippines; Newborn Hearing Screening Reference Center, University of the Philippines Manila-Philippine General Hospital, Manila, Philippines; University of the Philippines Manila-National Institutes of Health, University of the Philippines Manila-Philippine General Hospital, Manila, Philippines; Department of Otorhinolaryngology, University of the Philippines Manila-Philippine General Hospital, Manila, Philippines; Department of Pediatrics, University of the Philippines Manila-Philippine General Hospital, Manila, Philippines; MED-EL, Innsbruck, Austria; Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States; Department of Genetics, University of North Carolina, Chapel Hill, NC, United States; Office of Population Studies Foundation, United States; Department of Anthropology. Sociology and History, University of San Carlos, Cebu, Philippines; Department of Otolaryngology, University of Colorado, School of Medicine, Aurora, CO, United States
