Clue to a New Deafness Gene: A Large Chinese Nonsyndromic Hearing Loss Family Linked to DFNA4

Zong, Lei; Lu, Chunye; Zhao, Yongqiang; Li, Qian; Han, Dongyi; Wei, Yang; Shen, Yan; Zheng, Qingyin; Wang, Qiuju

doi:10.1016/j.jgg.2012.11.002

Cited by 6 publications

(5 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, we successfully established an experimental cholesteatoma model in mice using a modified protocol for autologous metal skin graftimplantation plus P. aeruginosa infection. The clinical features of experimental cholesteatomas were evaluated by endoscopic and anatomical microscopic examinations, auditory brainstem response (ABR) threshold evaluations, and histological analysis, as previously reported 28 29 . TLR4 deficiency resulted in markedly reduced bone destruction scores and less hearing loss compared with those in TLR2−/− and WT mice.…”

Section: Discussionmentioning

confidence: 99%

“…The ABR was measured in each mouse prior to the operation and at six weeks postoperatively. The ABR thresholds of the mice were tested using a computer-aided evoked potential system, as previously described 28 . Click, 8-kHz, and 16-kHz pure-tone burst stimuli were delivered to the right ears of mice in a sound-isolated and electrically shielded booth (Acoustic Systems, Austin, TX, USA) via a Beyer earphone.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

TLR4 drives the pathogenesis of acquired cholesteatoma by promoting local inflammation and bone destruction

Chen

et al. 2015

Sci Rep

View full text Add to dashboard Cite

Acquired cholesteatoma is a chronic inflammatory disease characterized by both hyperkeratinized squamous epithelial overgrowth and bone destruction. Toll-like receptor (TLR) activation and subsequent inflammatory cytokine production are closely associated with inflammatory bone disease. However, the expression and function of TLRs in cholesteatoma remain unclear.We observed inflammatory cell infiltration of the matrix and prematrix of human acquired cholesteatoma, as well as dramatically increased expression of TLR4 and the pro-inflammatory cytokines TNF-α and IL-1β. TLR2 exhibited an up-regulation that was not statistically significant. TLR4 expression in human acquired cholesteatoma correlated with disease severity; the number of TLR4-positive cells increased with an increased degree of cholesteatoma, invasion, bone destruction, and hearing loss. Moreover, TLR4 deficiency was protective against experimental acquired cholesteatoma-driven bone destruction and hearing loss, as it reduced local TNF-α and IL-1β expression and impaired osteoclast formation by decreasing expression of the osteoclast effectors receptor activator of nuclear factor (NF)-κB ligand (RANKL) and tartrate-resistant acid phosphatase (TRAP). TLR2 deficiency did not relieve disease severity, inflammatory responses, or osteoclast formation. Moreover, neither TLR2 nor TLR4 deficiency had an effect on antimicrobial peptides, inducible iNOS,BD-2 expression or bacterial clearance. Therefore, TLR4 may promote cholesteatoma-induced bone destruction and deafness by enhancing inflammatory responses and osteoclastogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

TLR4 drives the pathogenesis of acquired cholesteatoma by promoting local inflammation and bone destruction

Chen

et al. 2015

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The presence of cytoskeleton proteins and especially myosin-14 in TCs confirms this hypothesis. Taking into account that myosin-14 is known to be involved in sensory perception 54 , we can propose TCs as candidates for a mechanical sensing and mechanochemical conversion task . In addition, the presence of TC primary cilia was reported in vasculature 55 and trachea 56 , functioning as mechano- or chemosensors 57 , probably involved in the initiation of cellular global positioning to initiate tissue renewal after damage 58 .…”

Section: Discussionmentioning

confidence: 99%

Comparative proteomic analysis of human lung telocytes with fibroblasts

Zheng

Crețoiu

Yan

et al. 2014

J Cellular Molecular Medi

View full text Add to dashboard Cite

Telocytes (TCs) were recently described as interstitial cells with very long prolongations named telopodes (Tps; http://www.telocytes.com). Establishing the TC proteome is a priority to show that TCs are a distinct type of cells. Therefore, we examined the molecular aspects of lung TCs by comparison with fibroblasts (FBs). Proteins extracted from primary cultures of these cells were analysed by automated 2-dimensional nano-electrospray ionization liquid chromatography tandem mass spectrometry (2D Nano-ESI LC-MS/MS). Differentially expressed proteins were screened by two-sample t-test (P < 0.05) and fold change (>2), based on the bioinformatics analysis. We identified hundreds of proteins up- or down-regulated, respectively, in TCs as compared with FBs. TC proteins with known identities are localized in the cytoskeleton (87%) and plasma membrane (13%), while FB up-regulated proteins are in the cytoskeleton (75%) and destined to extracellular matrix (25%). These identified proteins were classified into different categories based on their molecular functions and biological processes. While the proteins identified in TCs are mainly involved in catalytic activity (43%) and as structural molecular activity (25%), the proteins in FBs are involved in catalytic activity (24%) and in structural molecular activity, particularly synthesis of collagen and other extracellular matrix components (25%). Anyway, our data show that TCs are completely different from FBs. In conclusion, we report here the first extensive identification of proteins from TCs using a quantitative proteomics approach. Protein expression profile shows many up-regulated proteins e.g. myosin-14, periplakin, suggesting that TCs might play specific roles in mechanical sensing and mechanochemical conversion task, tissue homoeostasis and remodelling/renewal. Furthermore, up-regulated proteins matching those found in extracellular vesicles emphasize TCs roles in intercellular signalling and stem cell niche modulation. The novel proteins identified in TCs will be an important resource for further proteomic research and it will possibly allow biomarker identification for TCs. It also creates the premises for understanding the pathogenesis of some lung diseases involving TCs.

show abstract

“… 19 Subsequently, the second family from Germany (Leipzig 9) and then several other families around the world were identified whose mutations could be mapped to DFNA4 locus. 20 - 24 Because the MYH14 gene, encoding a non-muscle myosin heavy-chain, was the first gene known to correspond to DFNA4, we sequenced it in the probands of family SY-026 and no pathogenic mutation was revealed. Then, we performed exome sequencing analysis on 4 family members and successfully identified a c.505G>A (p.G169R) in exon 3 of the CEACAM16 gene.…”

Section: Discussionmentioning

confidence: 99%

Exome sequencing identifies a novel CEACAM16 mutation associated with autosomal dominant nonsyndromic hearing loss DFNA4B in a Chinese family

Wang

et al. 2015

J Hum Genet

View full text Add to dashboard Cite

Autosomal dominant nonsyndromic hearing loss (ADNSHL/DFNA) is a highly genetically heterogeneous disorder. Hitherto only about 30 ADNSHL-causing genes have been identified and many unknown genes remain to be discovered. In this research, genome-wide linkage analysis mapped the disease locus to a 4.3 Mb region on chromosome 19q13 in SY-026, a five-generation nonconsanguineous Chinese family affected by late-onset and progressive ADNSHL. This linkage region showed partial overlap with the previously reported DFNA4. Simultaneously, probands were analyzed using exome capture followed by next generation sequencing. Encouragingly, a heterozygous missense mutation, c.505G>A (p.G169R) in exon 3 of the CEACAM16 gene (carcinoembryonic antigen-related cell adhesion molecule 16), was identified via this combined strategy. Sanger sequencing verified that the mutation co-segregated with hearing loss in the family and that it was not present in 200 unrelated control subjects with matched ancestry. This is the second report in the literature of a family with ADNSHL caused by CEACAM16 mutation. Immunofluorescence staining and Western blots also prove CEACAM16 to be a secreted protein. Furthermore, our studies in transfected HEK293T cells show that the secretion efficacy of the mutant CEACAM16 is much lower than that of the wild-type, suggesting a deleterious effect of the sequence variant.

show abstract

Clue to a New Deafness Gene: A Large Chinese Nonsyndromic Hearing Loss Family Linked to DFNA4

Cited by 6 publications

References 23 publications

TLR4 drives the pathogenesis of acquired cholesteatoma by promoting local inflammation and bone destruction

TLR4 drives the pathogenesis of acquired cholesteatoma by promoting local inflammation and bone destruction

Comparative proteomic analysis of human lung telocytes with fibroblasts

Exome sequencing identifies a novel CEACAM16 mutation associated with autosomal dominant nonsyndromic hearing loss DFNA4B in a Chinese family

Contact Info

Product

Resources

About