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Efficient Molecular Genetic Diagnosis of Enlarged Vestibular Aqueducts in East Asians

Cited 18 time in Web of Science Cited 21 time in Scopus
Authors
Choi, Byung Yoon; Stewart, Andrew K.; Cha, Won Jae; Seong, Moon-Woo; Nishimura, Katherine K.; Park, Sung Sup; Park, Shi-Nae; Kim, Chong-Sun; Oh, Seung-Ha; Griffith, Andrew J.; Alper, Seth L.; Chang, Sun O.; Chung, Jong Woo; Kim, Seung Won
Issue Date
2009-10
Publisher
MARY ANN LIEBERT INC
Citation
GENETIC TESTING AND MOLECULAR BIOMARKERS; Vol.13 5; 679-687
Abstract
Context: Enlargement of the vestibular aqueduct (EVA) is a commonly detected inner ear anomaly related to hearing loss and often associated with mutations of SLC26A4 encoding pendrin, a transmembrane exchanger of Cl(-), I(-), and HCO(3)(-). Here we describe the phenotypes of 27 Korean EVA subjects and their SLC26A4 genotypes determined by bidirectional nucleotide sequencing. Results: The detected variants include two novel missense substitutions (p. V138L and p. P542R). We characterized the ability of p. V138L and p. P542R pendrin products to traffic to the plasma membrane in COS-7 cells and to transport Cl(-), I(-), and HCO3- in Xenopus oocytes. The results indicate that p. P542R is a benign polymorphic variant, whereas p. V138L is a pathogenic mutation. Since this and other studies of East Asian EVA cohorts show that the majority of SLC26A4 mutations affect either or both of two amplicons (exons 7-8 and 19), we developed a hierarchical protocol that integrates direct sequencing with denaturing high-performance liquid chromatography analyses for detection of SLC26A4 mutations in these populations. We validated the cost efficiency of the integrated protocol by a simulated screen of published East Asian EVA cohorts with known SLC26A4 genotypes. Conclusions: Our study further defines the spectrum of SLC26A4 mutations among East Asians and demonstrates a rapid and efficient protocol for their detection.
ISSN
1945-0265
Language
English
URI
https://hdl.handle.net/10371/76292
DOI
https://doi.org/10.1089/gtmb.2009.0054
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College of Medicine/School of Medicine (의과대학/대학원)Laboratory Medicine (검사의학전공)Journal Papers (저널논문_검사의학전공)
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