Flat Threshold and Mid-Frequency Hearing Impairment in a Dutch DFNA8/12 Family with a Novel Mutation in &lt;i&gt;TECTA&lt;/i&gt;

Heer, Anne-Martine R. de; Pauw, Robert Jan; Huygen, P.L.M.; Collin, Rob W.J.; Kremer, Hannie; Cremers, C.W.R.J.

doi:10.1159/000171477

Cited by 14 publications

(11 citation statements)

References 51 publications

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“…24 -26 An overview of the various TECTA mutations that cause DFNA8/12 is presented in Figure 3c. The synonymous change described in this study, similar to missense mutations in the ZP domain, causes mid-frequency or flat threshold hearing impairment (de Heer et al, 8 submitted). The 37 amino acids that are absent in the mutant protein owing to the aberrant splicing event are located just N-terminally of the ZP domain.…”

Section: Resultsmentioning

confidence: 59%

Mid-frequency DFNA8/12 hearing loss caused by a synonymous TECTA mutation that affects an exonic splice enhancer

et al. 2008

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Autosomal dominant hearing loss is highly heterogeneous. Hearing impairment mainly involves the midfrequencies (500 -2000 Hz) in only a low percentage of the cases. In a Dutch family with autosomal dominant mid-frequency/flat hearing loss, genome-wide SNP analysis combined with fine mapping using microsatellite markers mapped the defect to the DFNA8/12 locus, with a maximum two-point LOD score of 3.52. All exons and intron -exon boundaries of the TECTA gene, of which mutations are causative for DFNA8/12, were sequenced. Only one heterozygous synonymous change in exon 16 (c.5331G4A; p.L1777L) was found to segregate with the hearing loss. This change was predicted to cause the loss of an exonic splice enhancer (ESE). RT-PCR using primers flanking exon 16 revealed, besides the expected PCR product from the wild-type allele, a smaller fragment only in the affected individual, representing part of an aberrant TECTA transcript lacking exon 16. The aberrant splicing is predicted to result in a deletion of 37 amino acids (p.S1758Y/G1759_N1795del) in a-tectorin. Subsequently, the same mutation was detected in two out of 36 individuals with a comparable phenotype. Owing to the position of the protein deletion just N-terminal of the zona pellucida (ZP) domain of a-tectorin, it is likely that the deletion of 37 amino acids may affect the proteolytic processing, structure and/or function of this domain, which results in a clinical phenotype comparable to that of missense mutations in the ZP domain. In addition, this is the first report of a synonymous mutation that affects an ESE and causes hereditary hearing loss.

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Section: Resultsmentioning

confidence: 59%

Mid-frequency DFNA8/12 hearing loss caused by a synonymous TECTA mutation that affects an exonic splice enhancer

et al. 2008

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“…[3][4][5][6][7][8][9][10] This gene encodes a-tectorin, the major component of noncollagenous glycoprotein of the tectorial membrane that consists of an extracellular matrix overlying the organ of corti, contacting the outer cochlear hair cells, and having a role in intracochlear sound transmission. 11 The a-tectorin is composed of three distinct modules: the entactin G1 domain, the zonadhesin (ZA) domain with von Willebrand factor type D repeats and the zona pellucida (ZP) domain.…”

Section: Introductionmentioning

confidence: 99%

TECTA mutations in Japanese with mid-frequency hearing loss affected by zona pellucida domain protein secretion

et al. 2012

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TECTA gene encodes a-tectorin, the major component of noncollagenous glycoprotein of the tectorial membrane, and has a role in intracochlear sound transmission. The TECTA mutations are one of the most frequent causes of autosomal dominant (AD) hearing loss and genotype-phenotype correlations are associated with mutations of TECTA in exons according to a-tectorin domains. In this study, we investigated the prevalence of hearing loss caused by TECTA mutations in Japanese AD hearing loss families, and confirmed genotype-phenotype correlation, as well as the intracellular localization of missense mutations in the a-tectorin domain. TECTA mutations were detected in 2.9% (4/139) of our Japanese AD hearing loss families, with the prevalence in moderate hearing loss being 7.7% (4/52), and all patients showed typical genotype-phenotype correlations as previously described. The present in vitro study showed differences of localization patterns between wild type and mutants, and suggested that each missense mutation may lead to a lack of assembly of secretion, and may reduce the incorporation of a-tectorin into the tectorial membrane.

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“…In addition, different audiogram patterns might confound the relationship between candidate gene polymorphisms and ARHI [16,48]. The genotypes of IQGAP2 did not show a significant effect on ARHI in different audiogram patterns after adjustment for other variables in group 70?.…”

Section: Discussionmentioning

confidence: 91%

The European GWAS-identified risk SNP rs457717 within IQGAP2 is not associated with age-related hearing impairment in Han male Chinese population

Luo

Shen

et al. 2015

Eur Arch Otorhinolaryngol

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This study aimed to test the association between the European GWAS-identified risk IQGAP2 SNP rs457717 (A>G) and age-related hearing impairment (ARHI) in a Han male Chinese (HMC) population. A total of 2420 HMC subjects were divided into two groups [group 70+: >70 years (n = 1306), and group 70-: ≤70 years (n = 1114)]. The participants were categorised into case and control groups according to Z high scores for group 70- and the severity of hearing loss and different audiogram shapes identified by K-means cluster analysis for group 70+. The IQGAP2 tagSNP rs457717 was genotyped in accordance with the different ARHI phenotypes. The genotype distributions of IQGAP2 (AA/AG/GG) were not significantly different between the case and control groups (P = 0.613 for group 70-; P = 0.602 for group 70+). Compared with genotype AA, the ORs of genotypes AG and GG for ARHI were not significantly different following adjustment for other environmental risk factors. We demonstrated that the IQGAP2 TagSNP rs457717 (A/G) was not associated with ARHI in HMC individuals.

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Flat Threshold and Mid-Frequency Hearing Impairment in a Dutch DFNA8/12 Family with a Novel Mutation in <i>TECTA</i>

Cited by 14 publications

References 51 publications

Mid-frequency DFNA8/12 hearing loss caused by a synonymous TECTA mutation that affects an exonic splice enhancer

Mid-frequency DFNA8/12 hearing loss caused by a synonymous TECTA mutation that affects an exonic splice enhancer

TECTA mutations in Japanese with mid-frequency hearing loss affected by zona pellucida domain protein secretion

The European GWAS-identified risk SNP rs457717 within IQGAP2 is not associated with age-related hearing impairment in Han male Chinese population

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