Mild and Variable Audiometric and Vestibular Features in a Third DFNA15 Family with a Novel Mutation in <i>POU4F3</i>

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

doi:10.1177/000348940911800413

Cited by 12 publications

(13 citation statements)

References 30 publications

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“…In such a case, basal turn gene expression may fall below some critical level more rapidly compared with apical turn because of a gradient of gene expression greater in the apex than in the base, resulting in progressive high frequency hearing loss. This speculation is consistent with the reported hearing loss types (such as high frequency progressive) in patients with the POU4F3 [11], [12], SLC17A8 [13], TMC1 [14], [15], and CRYM [16] mutations.…”

Section: Discussionsupporting

confidence: 91%

Deafness Gene Expression Patterns in the Mouse Cochlea Found by Microarray Analysis

et al. 2014

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BackgroundTonotopy is one of the most fundamental principles of auditory function. While gradients in various morphological and physiological characteristics of the cochlea have been reported, little information is available on gradient patterns of gene expression. In addition, the audiograms in autosomal dominant non syndromic hearing loss can be distinctive, however, the mechanism that accounts for that has not been clarified. We thought that it is possible that tonotopic gradients of gene expression within the cochlea account for the distinct audiograms.Methodology/Principal FindingsWe compared expression profiles of genes in the cochlea between the apical, middle, and basal turns of the mouse cochlea by microarray technology and quantitative RT-PCR. Of 24,547 genes, 783 annotated genes expressed more than 2-fold. The most remarkable finding was a gradient of gene expression changes in four genes (Pou4f3, Slc17a8, Tmc1, and Crym) whose mutations cause autosomal dominant deafness. Expression of these genes was greater in the apex than in the base. Interestingly, expression of the Emilin-2 and Tectb genes, which may have crucial roles in the cochlea, was also greater in the apex than in the base.Conclusions/SignificanceThis study provides baseline data of gradient gene expression in the cochlea. Especially for genes whose mutations cause autosomal dominant non syndromic hearing loss (Pou4f3, Slc17a8, Tmc1, and Crym) as well as genes important for cochlear function (Emilin-2 and Tectb), gradual expression changes may help to explain the various pathological conditions.

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Section: Discussionsupporting

confidence: 91%

Deafness Gene Expression Patterns in the Mouse Cochlea Found by Microarray Analysis

et al. 2014

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“…It plays an essential role for the normal development and proper function of inner ear hair cells. Mutations of the POU4F3 are associated with an adult‐onset, non‐syndromic, autosomal dominant progressive hearing impairment in humans [Vahava et al, 1998; Collin et al, 2008; de Heer et al, 2009; Lee et al, 2010]. So far, the patient was not found to have hearing problem, but his father was found to have progressive hearing loss, which can be attributed to the haploinsufficiency of the POU4F3 .…”

Section: Discussionmentioning

confidence: 99%

Identification of two inherited copy number variants in a male with autism supports two‐hit and compound heterozygosity models of autism

Gau

Liao

Hong

et al. 2012

American J of Med Genetics Pt B

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Autism is a childhood‐onset neurodevelopmental disorder with complex genetic mechanism underlying its etiology. Recent studies revealed that a few single de novo copy number variants of genomic DNA (copy number variants [CNVs]) are pathogenic and causal in some sporadic cases, adding support to the hypothesis that some sporadic autism might be caused by single rare mutation with large clinical effect. In this study, we report the detection of two novel private CNVs simultaneously in a male patient with autism. These two CNVs include a microduplication of ∼4.5 Mb at chromosome 4q12‐13.1 that was transmitted from his mother and a microdeletion of ∼1.8 Mb at 5q32 that was transmitted from his father. Several genes such as LPHN3, POU4F3, SH3RF2, and TCERG1 mapped to these two regions have psychiatric implications. However, the parents had only mild degree of attention deficit symptoms but did not demonstrate any obvious autistic symptoms or psychopathology. Our findings indicate that each of these two CNVs alone may not be pathogenic enough to cause clinical symptoms in their respective carriers, and hence they can be transmitted within each individual family. However, concomitant presence of these two CNVs might result in the clinical phenotypes of the affected patient reported here. Thus, our report of this family may represent an example to show that two hits of CNV and the presence of compound heterozygosity might be important mechanisms underlying the pathogenesis of autism. © 2012 Wiley Periodicals, Inc.

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“…Hwang et al (2009) also tried to link central obesity and audiogram patterns. More recently, de Heer et al (2009ade Heer et al ( , 2009bde Heer et al ( , 2009c have worked to relate age and genes to specifi c audiogram shapes. Such a growing body of literature justifi es a possible connection between audiogram shape and hearing loss etiology, and stresses the need to pay more attention to the audiogram confi guration.…”

Section: Sumariomentioning

confidence: 99%

Using cluster analysis to classify audiogram shapes

Lee

Hwang

Hou

et al. 2010

International Journal of Audiology

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The purpose of this study was to design a statistical classification system of audiogram shapes in order to improve and integrate shape recognition across clinical settings. The study included 1633 adult subjects with normal hearing or symmetric sensorineural hearing impairment who underwent pure-tone audiometry between July 2007 and December 2008. K-means cluster analysis was employed to categorize audiometric shapes. Eleven audiogram shapes were identified: rising, flat, peaked 8-kHz dip, 4-kHz dip, 8-kHz dip, mild sloping, severe 8-kHz dip, sloping, abrupt loss, severe sloping, and profound abrupt loss. By using the classification system and nomenclature identified for audiogram shapes as outlined in this study, errors based on personal experiences can be reduced and a consistency can be developed across clinics.

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Mild and Variable Audiometric and Vestibular Features in a Third DFNA15 Family with a Novel Mutation in POU4F3

Abstract: The clinical features in the present family with a POU4F3 mutation were fairly similar to those in the 2 previously described DFNA15 families, but the level of hearing impairment was milder, and there was no substantial vestibular dysfunction.

Cited by 12 publications

References 30 publications

Deafness Gene Expression Patterns in the Mouse Cochlea Found by Microarray Analysis

Deafness Gene Expression Patterns in the Mouse Cochlea Found by Microarray Analysis

Identification of two inherited copy number variants in a male with autism supports two‐hit and compound heterozygosity models of autism

Using cluster analysis to classify audiogram shapes

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