Evidence of a founder effect for the 235delC mutation of GJB2 (connexin�26) in east Asians

Yan, Denise; Park, Hong Joon; Ouyang, Xiao Mei; Pandya, Arti; Doi, Kunio; Erdenetungalag, Raadnabazar; Du, Li; Matsushiro, Naoki; Nance, Walter E.; Griffith, Andrew J.; Liu, Xue Zhong

doi:10.1007/s00439-003-1018-1

Cited by 98 publications

(108 citation statements)

References 35 publications

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“…25 The role of the founder effect in the origin and distribution of several mutations of the GJB2 gene was well established. 7, [26][27][28][29][30] Furthermore, novel hypotheses for the probable specific mechanism (combination of improved genetic fitness and assortative mating) for selective amplification of the commonest form of recessive deafness in the populations and of probable heterozygote advantage of GJB2 recessive mutations have been suggested. 31,32 Data on the mutation spectrum and prevalence of major mutations of the GJB2 gene in various ethnic groups are very important for the development of molecular diagnostics tools for identifying genetic causes of hereditary hearing loss; however, data on the prevalence of major GJB2 mutations in some populations are still not available.…”

Section: Introductionmentioning

confidence: 99%

Carrier frequency of GJB2 gene mutations c.35delG, c.235delC and c.167delT among the populations of Eurasia

Dzhemileva

Barashkov²,

Posukh

et al. 2010

J Hum Genet

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Section: Introductionmentioning

confidence: 99%

Carrier frequency of GJB2 gene mutations c.35delG, c.235delC and c.167delT among the populations of Eurasia

Dzhemileva

Barashkov²,

Posukh

et al. 2010

J Hum Genet

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“…However, a few GJB2 mutations have been described to be associated with autosomal dominant hearing loss [5]. Among the recessive mutations, 35delG is the most frequent in Caucasians, 167delT in Ashkenazi Jews, 235delC in East Asians, and R143W in Africans, suggesting the existence of founder effects in different ethnic groups [6][7][8][9][10][11][12][13][14][15][16][17][18]. In addition, some studies have shown the high prevalence of the IVS1 + 1G to A mutation in the non-coding part of the GJB2 gene [19,20].…”

Section: Introductionmentioning

confidence: 99%

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

Lee

Choi

Bae

et al. 2008

International Journal of Pediatric Otorhinolaryngology

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Objective-Mutations in the GJB2, GJB6 and SLC26A4 genes are a frequent cause of hearing loss in a number of populations. However, little is known about the genetic causes of hearing loss in the Korean population.Methods-We sequenced the GJB2 and GJB6 genes to examine the role of mutations in these genes in twenty-two hearing loss patients. We also sequenced the SLC26A4 gene in seven patients with inner ear malformations, including enlarged vestibular aqueduct (EVA) revealed by computer tomography.Results-Coding sequence mutations in GJB2 were identified in 13.6% of the patients screened. Two different mutations, 235delC and T86R were found in three unrelated patients. The 235delC was the most prevalent mutation with an allele frequency of 6.9% in our patient group. No mutations, including 342 kb deletion, were found in GJB6 gene. Three different variants of SLC26A4 were identified in the EVA patients, including one novel mutation. Four EVA patients carried two mutant alleles of SLC26A4, and at least one allele in all patients was the H723R mutation, which accounted for 75% of all mutant alleles.Conclusions-Our results suggest that GJB2 and SLC26A4 mutations together make up a major cause of congenital hearing loss in the Korean population. Further studies may be able to identify other common variants that account for a significant fraction of hearing loss in the Korean population.

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“…During data analyses, we have found that many well-known deafness-causing mutations are present in the dbSNP database. One of the best examples is rs80338943, which is the most common GJB2 deafness mutation (235delC) among the East Asians (Yan et al, 2003). There is definitely an urgent need for better SNP filters and annotation for helping find deleterious deafness mutations.…”

Section: Discussionmentioning

confidence: 99%

A Low-Cost Exon Capture Method Suitable for Large-Scale Screening of Genetic Deafness by the Massively-Parallel Sequencing Approach

Tang

Qian

Ahmad

et al. 2012

Genetic Testing and Molecular Biomarkers

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Current major barriers for using next-generation sequencing (NGS) technologies in genetic mutation screening on an epidemiological scale appear to be the high accuracy demanded by clinical applications and high persample cost. How to achieve high efficiency in enriching targeted disease genes while keeping a low cost/sample is a key technical hurdle to overcome. We validated a cDNA-probe-based approach for capturing exons of a group of genes known to cause deafness. Polymerase chain reaction amplicons were made from cDNA clones of the targeted genes and used as bait probes in hybridization for capturing human genomic DNA (gDNA) fragments. The cDNA library containing the clones of targeted genes provided a readily available, low-cost, and regenerable source for producing capture probes with standard molecular biology equipment. Captured gDNA fragments by our method were sequenced by the Illumina NGS platform. Results demonstrated that targeted exons captured by our approach achieved specificity, multiplexicity, uniformity, and depth of coverage suitable for accurate sequencing applications by the NGS systems. Reliable genotype calls for various homozygous and heterozygous mutations were achieved. The results were confirmed independently by conventional Sanger sequencing. The method validated here could be readily expanded to include all-known deafness genes for applications such as genetic hearing screening in newborns. The high coverage depth and cost benefits of the cDNA-probe-based exon capture approach may also facilitate widespread applications in clinical practices beyond screening mutations in deafness genes.

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Evidence of a founder effect for the 235delC mutation of GJB2 (connexin�26) in east Asians

Cited by 98 publications

References 35 publications

Carrier frequency of GJB2 gene mutations c.35delG, c.235delC and c.167delT among the populations of Eurasia

Carrier frequency of GJB2 gene mutations c.35delG, c.235delC and c.167delT among the populations of Eurasia

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

A Low-Cost Exon Capture Method Suitable for Large-Scale Screening of Genetic Deafness by the Massively-Parallel Sequencing Approach

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