Clinical characteristics and genotype–phenotype correlation of hearing loss patients withSLC26A4mutations

Suzuki, Hiroaki; Oshima, Aki; Tsukamoto, Koji; Abe, Satoko; Kumakawa, Kozo; Nagai, Kyoko; Satoh, Hitoshi; Kanda, Yukihiko; Iwasaki, Satoshi; Usami, Shin‐ichi

doi:10.1080/00016480701258739

Cited by 57 publications

(46 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, Suzuki et al [2007] compared the hearing severity and the presence of goiter according to the genotypes in 39 Japanese EVA patients with biallelic SLC26A4 mutations, and did not identify a clear correlation between SLC26A4 genotypes and phenotypes. The results of the present study are in accordance with those of Suzuki et al [2007], but appear to some extent different from those of the Pryor et al [2005] and Azaiez et al [2007] series. The discrepancies among these studies might be attributed to the subjects enrolled and the method adopted for investigating the genotype-phenotype correlations.…”

Section: Discussionmentioning

confidence: 99%

“…Different from Pryor et al [2005] and Azaiez et al [2007] who compared SL-C26A4 genotypes according to different phenotypes (i.e. Pendred syndrome and nonsyndromic EVA), Suzuki et al [2007] and the present study compared phenotypes (i.e. goiter, IEM or audiological results) according to the SLC26A4 genotypes.…”

Section: Discussionmentioning

confidence: 99%

“…First, as a disease entity inherited in an autosomal recessive manner, none or only 1 mutated SL-C26A4 allele could be identified in many families [Albert et al, 2006;Azaiez et al, 2007;Blons et al, 2004;Campbell et al, 2001;Coyle et al, 1998;Park et al, 2005;Pryor et al, 2005;Tsukamoto et al, 2003;Wu et al, 2005b], resulting in uncertainties in the underlying pathology and genetic counseling of these families. Second, environmental or other genetic factors are involved in the expression of the disease, thus confounding the correlation between SLC26A4 genotypes and phenotypes and impeding the prediction of prognosis by genetic diagnosis [Azaiez et al, 2007;Pryor et al, 2005;Suzuki et al, 2007;Wu et al, 2005b]. Recently, the transcriptional control of SLC26A4 has been reported to contribute to the pathogenesis of nonsyndromic EVA and Pendred syndrome [Yang et al, 2007].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Phenotypic Analyses and Mutation Screening of the SLC26A4 and FOXI1 Genes in 101 Taiwanese Families with Bilateral Nonsyndromic Enlarged Vestibular Aqueduct (DFNB4) or Pendred Syndrome

Wu¹,

Lu²,

Chen

et al. 2009

Audiol Neurotol

View full text Add to dashboard Cite

Recessive mutations in the SLC26A4 gene are responsible for nonsyndromic enlarged vestibular aqueduct (EVA) and Pendred syndrome. However, in some affected families, only 1 or 0 mutated allele can be identified, as well as no clear correlation between SLC26A4 genotypes and clinical phenotypes, hampering the accuracy of genetic counseling. To elucidate the genetic composition of nonsyndromic EVA and Pendred syndrome, we screened related genomic fragments, including the SLC26A4 coding regions, the SLC26A4 promoter and the FOXI1 transcription factor gene, in 101 Taiwanese families, and analyzed their phenotypic and genotypic results. Mutation screening in the SLC26A4 coding regions by direct sequencing and quantitative polymerase chain reaction detected 2 mutations in 63 (62%) families, 1 mutation in 24 (24%) families and no mutation in 14 (14%) families. The radiological findings, the presence of goiters and the audiological results were not different among probands (i.e. index cases of the families) with different SLC26A4 genotypes. Specifically, probands heterozygous for SLC26A4 mutations demonstrated clinical features indistinguishable from those of probands with 2 mutated alleles, implicating that there might be undetected mutations. However, except for a variant (c.–2554G>A of SLC26A4) with possible pathological consequences, no definite mutation was detected after extensive screening in the SLC26A4 promoter and FOXI1. In other words, in most Taiwanese families nonsyndromic EVA or Pendred syndrome might not result from aberrance in the transcriptional control of SLC26A4 by FOXI1. Meanwhile, exploration of undetected mutations in the SLC26A4 noncoding regions revealed 9 divergent haplotypes among the 21 no-mutation-detected SLC26A4 alleles of the c.919-2A>G heterozygotes, indicating that there might be no common and predominant mutations in the SLC26A4 introns.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Phenotypic Analyses and Mutation Screening of the SLC26A4 and FOXI1 Genes in 101 Taiwanese Families with Bilateral Nonsyndromic Enlarged Vestibular Aqueduct (DFNB4) or Pendred Syndrome

Wu¹,

Lu²,

Chen

et al. 2009

Audiol Neurotol

View full text Add to dashboard Cite

show abstract

“…These phenotypes range from isolated NSHL to NS EVA to Mondini dysplasia to PS, suggesting that the same etiology underlies all conditions [21,24]. Furthermore, phenotypes are variable, even with the same mutations.…”

Section: Slc26a4 (Pds) Deafness Mutationsmentioning

confidence: 99%

Integration of Human and Mouse Genetics Reveals Pendrin Function in Hearing and Deafness

Dror

Brownstein²,

Avraham³

2011

Cell Physiol Biochem

View full text Add to dashboard Cite

Genomic technology has completely changed the way in which we are able to diagnose human genetic mutations. Genomic techniques such as the polymerase chain reaction, linkage analysis, Sanger sequencing, and most recently, massively parallel sequencing, have allowed researchers and clinicians to identify mutations for patients with Pendred syndrome and DFNB4 non-syndromic hearing loss. While thus far most of the mutations have been in the SLC26A4 gene coding for the pendrin protein, other genetic mutations may contribute to these phenotypes as well. Furthermore, mouse models for deafness have been invaluable to help determine the mechanisms for SLC26A4-associated deafness. Further work in these areas of research will help define genotype-phenotype correlations and develop methods for therapy in the future.

show abstract

“…Most of the genes associated with hereditary hearing loss are also expressed in the vestibular endorgans. However, only a limited number of genes, namely, COCH and SLC26A4, have been reported to be associated with vestibular dysfunctions and/or vertigo, [91][92][93][94] and the involvement of these genes remains unclear. In the vestibular system, mechanical transduction occurs by linear and rotatory acceleration.…”

Section: Gene Expression Profiles Of the Vestibular Endorgansmentioning

confidence: 99%

Gene Expression Profiles of the Cochlea and Vestibular Endorgans

Nishio

Hattori

Moteki

et al. 2015

Ann Otol Rhinol Laryngol

Self Cite

View full text Add to dashboard Cite

Objectives: We sought to elucidate the gene expression profiles of the causative genes as well as the localization of the encoded proteins involved in hereditary hearing loss. Methods: Relevant articles (as of September 2014) were searched in PubMed databases, and the gene symbols of the genes reported to be associated with deafness were located on the Hereditary Hearing Loss Homepage using localization, expression, and distribution as keywords. Results: Our review of the literature allowed us to systematize the gene expression profiles for genetic deafness in the inner ear, clarifying the unique functions and specific expression patterns of these genes in the cochlea and vestibular endorgans. Conclusions:The coordinated actions of various encoded molecules are essential for the normal development and maintenance of auditory and vestibular function.

show abstract

Clinical characteristics and genotype–phenotype correlation of hearing loss patients withSLC26A4mutations

Cited by 57 publications

References 20 publications

Phenotypic Analyses and Mutation Screening of the <i>SLC26A4</i> and <i>FOXI1</i> Genes in 101 Taiwanese Families with Bilateral Nonsyndromic Enlarged Vestibular Aqueduct (DFNB4) or Pendred Syndrome

Phenotypic Analyses and Mutation Screening of the <i>SLC26A4</i> and <i>FOXI1</i> Genes in 101 Taiwanese Families with Bilateral Nonsyndromic Enlarged Vestibular Aqueduct (DFNB4) or Pendred Syndrome

Integration of Human and Mouse Genetics Reveals Pendrin Function in Hearing and Deafness

Gene Expression Profiles of the Cochlea and Vestibular Endorgans

Contact Info

Product

Resources

About