RGD Reference Report - Efficient molecular genetic diagnosis of enlarged vestibular aqueducts in East Asians. - Rat Genome Database

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Efficient molecular genetic diagnosis of enlarged vestibular aqueducts in East Asians.

Authors: Choi, BY  Stewart, AK  Nishimura, KK  Cha, WJ  Seong, MW  Park, SS  Kim, SW  Chun, YS  Chung, JW  Park, SN  Chang, SO  Kim, CS  Alper, SL  Griffith, AJ  Oh, SH 
Citation: Choi BY, etal., Genet Test Mol Biomarkers. 2009 Oct;13(5):679-87. doi: 10.1089/gtmb.2009.0054.
RGD ID: 7411669
Pubmed: (View Article at PubMed) PMID:19645628
DOI: Full-text: DOI:10.1089/gtmb.2009.0054

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 HCO(3)(-) 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.

Disease Annotations    

Phenotype Annotations    

Human Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Slc26a4  (solute carrier family 26 member 4)

Genes (Mus musculus)
Slc26a4  (solute carrier family 26, member 4)

Genes (Homo sapiens)
SLC26A4  (solute carrier family 26 member 4)

Additional Information