Province Key Laboratory of Otolaryngology Critical Diseases

Changsha, China

Province Key Laboratory of Otolaryngology Critical Diseases

Changsha, China

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Yao Y.,Central South University | Yao Y.,Province Key Laboratory of Otolaryngology Critical Diseases | Xie S.,Central South University | Xie S.,Province Key Laboratory of Otolaryngology Critical Diseases | And 8 more authors.
European Archives of Oto-Rhino-Laryngology | Year: 2017

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a group of multifactorial and heterogeneous disorders with a significant economic strain on society, likely made up of different endotypes, each with a unique pathomechanism. In addition to the traditional clinical measures, there is a recognized need for reliable biomarkers to provide predictive information regarding diagnosis, endotypes, treatment responses, and future risk of recurrence. Fueled by the advances in basic research, various biomarkers have been explored in recent years. Biomarkers of CRSwNP can originate from a variety of sources, including nasal secretions, nasal biopsies, exhaled breath, and peripheral blood. In this review, we aim to summarize the existing and emerging biomarkers available for the evaluation and management of CRSwNP. Currently, eosinophil count in nasal mucosa has proved particularly valuable for endotyping, assessing disease severity, and predicting steroid responsiveness and surgical outcomes. Blood eosinophilia may be used as a surrogate for tissue eosinophilic inflammation, whereas its utility remains limited. Type 2 cytokines, such as IL-4, IL-5, and IL-13, and IgE have been identified as potential therapeutic targets. Moreover, matrix metalloproteinases (MMP)-9 is linked to healing quality after sinus surgery. Nasal nitric oxide (nNO) appears to fill the niche as a noninvasive measure for sinus ostial patency. In addition, recent data have shown some promising biomarkers involved in corticosteroid resistance and olfactory dysfunction. However, rigorous validation using large cohort studies is necessary before these biomarkers can be mainstreamed into clinical practice. © 2017 Springer-Verlag Berlin Heidelberg

Wang H.,Central South University | Wang H.,Province Key Laboratory of Otolaryngology Critical Diseases | Wang X.,Central South University | Wang X.,Province Key Laboratory of Otolaryngology Critical Diseases | And 28 more authors.
Journal of Human Genetics | Year: 2015

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. © 2015 The Japan Society of Human Genetics.

Zhang H.,Central South University | Zhang H.,Xinjiang Medical University | Luo H.,Central South University | Chen H.,Central South University | And 10 more authors.
FEBS Letters | Year: 2012

MITF mutations results in an abnormal melanocyte development and lead to Waardenburg syndrome type 2 (WS2). Here, we analyzed the in vitro activities of two recently identified WS2-associated MITF mutations (p.R217I and p.T192fsX18). The R217I MITF retained partial activity, normal DNA-binding ability and nuclear distribution, whereas the T192fsX18 MITF failed to activate TYR promoter and showed aberrant subcellular localization which may be caused by deletion of nuclear localization signal (NLS) at aa 213-218 (ERRRRF). These results suggest that haploinsufficiency may be the underlying mechanism for the mild phenotypes of WS2 caused by these two mutations. © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Zhang H.,Central South University | Zhang H.,Xinjiang Medical University | Chen H.,Central South University | Chen H.,Province Key Laboratory of Otolaryngology Critical Diseases | And 14 more authors.
Human Genetics | Year: 2012

Waardenburg syndrome (WS) is an auditory-pigmentary disorder resulting from melanocyte defects, with varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair, skin, and inner ear. WS is classified into four subtypes (WS1-WS4) based on additional symptoms. PAX3 and SOX10 are two transcription factors that can activate the expression of microphthalmia- associated transcription factor (MITF), a critical transcription factor for melanocyte development. Mutations of PAX3 are associated with WS1 and WS3, while mutations of SOX10 cause WS2 and WS4. Recently, we identified some novel WS-associated mutations in PAX3 and SOX10 in a cohort of Chinese WS patients. Here, we further identified an E248fsX30 SOX10 mutation in a family of WS2. We analyzed the subcellular distribution, expression and in vitro activity of two PAX3 mutations (p.H80D, p.H186fsX5) and four SOX10 mutations (p.E248fsX30, p.G37fsX58, p.G38fsX69 and p.R43X). Except H80D PAX3, which retained partial activity, the other mutants were unable to activate MITF promoter. The H80D PAX3 and E248fsX30 SOX10 were localized in the nucleus as wild type (WT) proteins, whereas the other mutant proteins were distributed in both cytoplasm and nucleus. Furthermore, E248fsX30 SOX10 protein retained the DNA-binding activity and showed dominant-negative effect on WT SOX10. However, E248fsX30 SOX10 protein seems to decay faster than the WT one, which may underlie the mild WS2 phenotype caused by this mutation. © Springer-Verlag 2011.

Wang H.-H.,Central South University | Wang H.-H.,Province Key Laboratory of Otolaryngology Critical Diseases | Chen H.-S.,Central South University | Chen H.-S.,Province Key Laboratory of Otolaryngology Critical Diseases | And 16 more authors.
Gene | Year: 2014

Waardenburg syndrome type IV (WS4) is a rare genetic disorder, characterized by auditory-pigmentary abnormalities and Hirschsprung disease. Mutations of the EDNRB gene, EDN3 gene, or SOX10 gene are responsible for WS4. In the present study, we reported a case of a Chinese patient with clinical features of WS4. In addition, the three genes mentioned above were sequenced in order to identify whether mutations are responsible for the case. We revealed a novel nonsense mutation, c.1063C>T (p.Q355*), in the last coding exon of SOX10. The same mutation was not found in three unaffected family members or 100 unrelated controls. Then, the function and mechanism of the mutation were investigated in vitro. We found both wild-type (WT) and mutant SOX10 p.Q355* were detected at the expected size and their expression levels are equivalent. The mutant protein also localized in the nucleus and retained the DNA-binding activity as WT counterpart; however, it lost its transactivation capability on the MITF promoter and acted as a dominant-negative repressor impairing function of the WT SOX10. © 2014 Elsevier B.V.

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