Genetic basis of hearing loss associated with enlarged vestibular aqueducts in Koreans

Abstract

Sensorineural hearing loss associated with enlargement of the vestibular aqueduct (EVA) can be associated with mutations of the SLC26A4 gene. In western populations, less than one-half of the affected individuals with EVA have two mutant SLC26A4 alleles, and EVA is frequently caused by unknown genetic or environmental factors alone or in combination with a single SLC26A4 mutation as part of a complex trait. In this study, we ascertained 26 Korean probands with EVA and performed nucleotide sequence analysis to detect SLC26A4 mutations. All subjects had bilateral EVA, and 20 of 26 were sporadic (simplex) cases. Fourteen different mutations were identified, including nine novel mutations. Five mutations were recurrent and accounted for 80% of all mutant alleles, providing a basis for the design and interpretation of cost-efficient mutation detection algorithms. Two mutant alleles were identified in 21 (81%), one mutant allele was detected in three (11%), and zero mutant allele was detected in two (8%) of 26 probands. The high proportion of Korean probands with two SLC26A4 mutations may reflect a reduced frequency of other genetic or environmental factors causing EVA in comparison to western populations.

Molecular analysis of the GJB2, GJB6 and SLC26A4 genes in Korean deafness patients

“…The Q421R mutation at the same position was reported in the study of Prasad et al (2004) [44] and the functional studies of the similar location such as T416P mutation suggest that the change of amino acid at this position occurred the cause of disease [45,46]. We demonstrated severe to profound hearing impairment in 7 patients with inner ear malformations, consistent with the results of previous studies [30,42]. The phenotypic features of SLC26A4 mutations are variable, ranging from typical PS to nonsyndromic recessive hearing loss associated with EVA (DFNB4).…”

“…In contrast, H723R, IVS7-2A>G, and IVS9+3A>G account for the majority of SLC26A4 mutations in East Asian populations. Combined with the results of Park et al (2004) and Cho et al (2006), our data indicate the H723R mutation accounts for approximately 40% of SLC26A4 mutations in Korea, which is similar to the 53% observed in Japanese patients [30,43]. Our observations confirm that H723R is the most frequently detected mutation in both Korean and Japanese populations, perhaps as a result of a common founder effect.…”

“…Such mutations account for approximately 5% of recessive hearing loss in Asians [29]. Moreover, Park et al (2004) have shown that a high proportion of Korean hearing loss patients with EVA have mutations of this gene, and five mutations account for 80% of all mutant alleles [30].…”

Application of allele-specific primer extension-based microarray for simultaneous multi-gene mutation screening in patients with non-syndromic hearing loss

“…Since most genetic studies in the Korean population have been focused on the GJB2, SLC26A4 and mitochondrial genes, we selected seven different mutations in these genes based on their high frequencies in the Korean population (6)(7)(8)10,(16)(17)(18). The carrier frequency of the GJB2 gene is estimated to be 3% in the Korean population, and the p.V37I, c.235delC and p.R143W mutations were frequently found in Korean patients (6,7,17).…”

“…Seven different mutations in the GJB2, SLC26A4 and mitochondrial 12S rRNA genes previously identified in a Korean population were selected for the genotyping microarray: the GJB2 p.V37I, p.R143W and c.235delC mutations; the SLC26A4 IVS7-2A>G, IVS9+3A>G and p.H723R mutations; and the mtDNA A1555G mutation (6,7,(16)(17)(18). A set of 14 probes with wild and mutant sequences was designed and printed on amine-coated glass slides (GAPSII slide cat# 40004, Corning, Acton, MA, USA) in triplicate using a MicroGrid Compact printer (BioRobotics, Apogent Discoveries, Hudson, NH, USA).…”