Loss of heterozygosity analysis of case No.1.

<p>A comparison of lymphocyte DNA and tumor DNA using the flanking, D22S268 and D22S275, and intragenic, D22S929, microsatellite markers in the <i>NF2</i> gene region. In case, three markers showed loss of heterozygosity by allele loss in the tumor DNA.</p

Loss of heterozygosity (LOH) and mutation in sporadic vestibular schwannomas.

<p>Loss of heterozygosity (LOH) and mutation in sporadic vestibular schwannomas.</p

Evaluation of the Contribution of the <i>EYA4</i> and <i>GRHL2</i> Genes in Korean Patients with Autosomal Dominant Non-Syndromic Hearing Loss

<div><p><i>EYA4</i> and <i>GRHL2</i> encode transcription factors that play an important role in regulating many developmental stages. Since <i>EYA4</i> and <i>GRHL2</i> were identified as the transcription factors for the DFNA10 and DFNA28, 8 <i>EYA4</i> mutations and 2 <i>GRHL2</i> mutations have been reported worldwide. However, these genes have been reported in few studies of the Korean population. In this study, we performed a genetic analysis of <i>EYA4</i> and <i>GRHL</i>2 in 87 unrelated Korean patients with autosomal dominant non-syndromic hearing loss (NSHL). A total of 4 genetic variants in the <i>EYA4</i> gene were identified, including the 2 nonsense mutations p.S288X and p.Q393X. The novel mutation p.Q393X (c.1177C>T) resulted in a change in the codon at amino acid position 393 from a glutamine to a stop codon. The p.Q393X allele was predicted to encode a truncated protein lacking the entire C-terminal Eya homolog region (Eya HR), which is essential for the interaction with the transcription factor SIX3. The p.S288X (c.863C>A) mutation was found in a Korean family from a previous study. We analyzed p.S288X-linked microsatellite markers and determined that p.S288X might be a founder mutation and a hotspot mutation in Koreans. In <i>GRHL2</i>, a total of 4 genetic variants were identified, but none were associated with hearing loss in Korean patients. This suggests that <i>GRHL2</i> may not be a main causal gene for autosomal dominant NSHL in Korean patients. In conclusion, our data provide fundamental information to predict the genotypes of Korean patients diagnosed with autosomal dominant NSHL.</p></div

Mutational Analysis of <i>EYA1</i>, <i>SIX1</i> and <i>SIX5</i> Genes and Strategies for Management of Hearing Loss in Patients with BOR/BO Syndrome

<div><p>Background</p><p>Branchio-oto-renal (BOR) or branchio-otic (BO) syndrome is one of the most common forms of autosomal dominant syndromic hearing loss. Mutations in <i>EYA1</i>, <i>SIX1</i> and <i>SIX5</i> genes have been associated with BOR syndrome. In this study, clinical and genetic analyses were performed in patients with BOR/BO syndrome focusing on auditory manifestations and rehabilitation.</p><p>Methods</p><p>The audiologic manifestations were reviewed in 10 patients with BOR/BO syndrome. The operative findings and hearing outcome were analyzed in patients who underwent middle ear surgeries. The modality and outcome of auditory rehabilitation were evaluated. Genetic analysis was performed for <i>EYA1</i>, <i>SIX1</i>, and <i>SIX5</i> genes.</p><p>Results</p><p>All patients presented with mixed hearing loss. Five patients underwent middle ear surgeries without successful hearing gain. Cochlear implantation performed in two patients resulted in significant hearing improvement. Genetic analysis revealed four novel <i>EYA1</i> mutations and a large deletion encompassing the <i>EYA1</i> gene.</p><p>Conclusions</p><p>Auditory rehabilitation in BOR/BO syndrome should be individually tailored keeping in mind the high failure rate after middle ear surgeries. Successful outcome can be expected with cochlear implantations in patients with BOR/BO syndrome who cannot benefit from hearing aids. The novel <i>EYA1</i> mutations may add to the genotypic and phenotypic spectrum of BOR syndrome in the East Asian population.</p></div

Human Taste Receptor-Functionalized Field Effect Transistor as a Human-Like Nanobioelectronic Tongue

In this study, we developed a human taste receptor protein, hTAS2R38-functionalized carboxylated polypyrrole nanotube (CPNT)-field effect transistor (FET) as a nanobioelectronic tongue (nbe-tongue) that displayed human-like performance with high sensitivity and selectivity. Taster type (PAV) and nontaster type (AVI) hTAS2R38s were expressed in <i>Escherichia coli</i> (<i>E. coli</i>) at a high level and immobilized on a CPNT-FET sensor platform. Among the various tastants examined, PAV-CPNT-FET exclusively responded to target bitterness compounds, phenylthiocarbamide (PTC) and propylthiouracil (PROP), with high sensitivity at concentrations as low as 1 fM. However, no significant changes were observed in the AVI-CPNT-FET in response to the target bitter tastants. This nbe-tongue exhibited different bitter-taste perception of compounds containing thiourea (N–CS) moieties such as PTC, PROP, and antithyroid toxin in vegetables, which corresponded to the haplotype of hTAS2R38 immobilized on CPNTs. This correlation with the type of receptor is very similar to the human taste system. Thus, the artificial taste sensor developed in this study allowed for the efficient detection of target tastants in mixture and real food sample with a human-like performance and high sensitivity. Furthermore, our nbe-tongue could be utilized as a substitute for cell-based assays and to better understand the mechanisms of human taste

Location of the p.S288X mutation in <i>EYA4</i> and linked STR markers on chromosome 6q.

<p>The physical map marks the location of 5 microsatellite markers and positions.</p

SNPs of the <i>GRHL2</i> gene identified in this study.

<p>SNPs of the <i>GRHL2</i> gene identified in this study.</p

Identification of three novel splice site mutations in the <i>EYA1</i> gene.

<p>The nucleotide sequences of the control (WT/WT) and the affected individuals (WT/MT) are shown for patients 5 (A), 6 (B), and 7 (C). Each heterozygous mutation is indicated by arrowheads. (A, C) The mutations c.1140+ G>A and c.699+5 G>A are splicing donor site mutations of exons 12 and 10, respectively. (B) The mutation c.1598-2G>A is splicing acceptor site mutation of exon 17.</p

The findings of temporal bone CT in patient 7 and normal control.

<p>(A–E) These images are temporal bone CT in patient 7. (A) Cochlear hypoplasia type III with less than two turns is indicated by a black arrow. (B) The vestibular aqueduct (white asterisk) was enlarged and seen in a circular shape in the axial view. The lateral semicircular canal was slightly hypoplastic and the vestibular was dilated (black arrowhead). (C) The facial nerve ran inferior to the hypoplastic cochlea and displayed an obtuse angle between the labyrinthine and tympanic segments (white arrowhead). (D) The modiolus (white arrow) was present but defective and hypoplastic. (E) The ossicular chain (white arrow) seen in the coronal view was positioned in a different angle compared to the normal control. (F–K) These images are temporal bone CT in normal control.</p

Five novel mutations identified in <i>EYA</i>1 gene.

<p>Five novel mutations identified in <i>EYA</i>1 gene.</p