Chen H.,Shanghai JiaoTong University |
Chen H.,Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases |
Zhu W.,Shanghai JiaoTong University |
Zhu W.,Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases |
And 8 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2017
Purpose: In addition to genetic alterations, the importance of a CpG island methylator phenotype, characterized by methylation of multiple tumour-suppressor genes (TSGs), has been acknowledged in many cancer types. This study was done to determine the impact of genetic and epigenetic patterns on the clinical characteristics of the head and neck paragangliomas (HNPGLs). Methods: The retrospective study examined a series of 37 patients with HNPGLs who underwent surgical resection between 2010 and 2015. The mutations in the succinate dehydrogenase (SDH) genes were detected using direct DNA sequencing. Aberrant hypermethylation of the CpG islands of a panel of ten TSGs was also analysed using methylation-specific PCR. Results: Direct sequencing demonstrated the presence of germline SDH mutations in ten HNPGLs. Comparisons of clinical features between mutated and non-mutated HNPGLs established an association of SDH mutations with progressive phenotypes, including an earlier formation, multiple lesions, or malignancy. There was also a significant correlation between the presence of SDH mutations and the number of TSGs methylated in HNPGLs. The SDH-related tumours were therefore more likely to suffer from a CpG island methylator phenotype. Four differentially methylated TSGs in mutated tumours vs non-mutated counterparts were identified with inefficient expression through Real-Time PCR analysis. Conclusions: Our results suggested that epigenetic inactivation on multiple TSGs may serve as a key mechanism for the progressive behaviors of SDH-mutated HNPGLs. Thus, an interplay between genetic status, epigenetic alterations, and clinical features might be established in the disease. © 2017 Springer-Verlag Berlin Heidelberg
Huo Z.,Shanghai JiaoTong University |
Huo Z.,Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases |
Zhang Z.,Shanghai JiaoTong University |
Zhang Z.,Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases |
And 10 more authors.
European Archives of Oto-Rhino-Laryngology | Year: 2016
Cystic vestibular schwannoma (CVS) is classified as Type A and Type B based on the overall cyst location and cyst wall thickness in magnetic resonance imaging. A retrospective analysis was performed to compare surgical considerations and outcomes between Type A and Type B groups of CVS. We selected 188 patients diagnostic for CVS with surgical resection, and divided them into Type A and Type B groups. General information, preoperative symptoms, the result of neuroimaging, and audiological tests were recorded. Surgical approach, completeness of tumor resection, and intraoperative facial nerve (FN) integrity were taken down. After operation, the short-term and long-term FN functions, complications, and recurrence rate were evaluated. The total tumor removal rate in Type A group was higher than that in Type B group (86.1 vs 72.5 %, p = 0.021). Anatomical FN integrity was preserved in 173 patients (92.0 %), with no significant differences between Type A and Type B. FN function was better in Type A group at hospital discharge. Besides, a good FN function rate was inversely proportional to the tumor size. The long-term FN function and all of the complications had no significant differences between the two groups. Patients in the Type B group are prone to have a lower total tumor removal rate and transient FN dysfunction. The long-term FN function was similar in both groups. Tumor size is another important indication of FN function. All postoperative complications occurred in patients with a tumor larger than grade 3, regardless of the subtypes of CVS. © 2016 Springer-Verlag Berlin Heidelberg
Chen Y.,Shanghai JiaoTong University |
Chen Y.,Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases |
Wang Z.,Shanghai JiaoTong University |
Wang Z.,Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases |
And 14 more authors.
PLoS ONE | Year: 2015
The mutation spectrum of deafness genes may vary in different ethnical groups. In this study, we investigated the genetic etiology of nonsyndromic deafness in four consanguineous and two multiplex Uyghur families in which mutations in common deafness genes GJB2, SLC26A4 and MT-RNR1 were excluded. Targeted next-generation sequencing of 97 deafness genes was performed in the probands of each family. Novel pathogenic mutations were identified in four probands including the p.L416R/p.A438T compound heterozygous mutations in TMC1, the homozygous p.V1880E mutation in MYO7A, c.1238delT frameshifting deletion in PCDH15 and c.9690+1G>A splice site mutation in MYO15A. Cosegregation of the mutations and the deafness were confirmed within each family by Sanger sequencing. No pathogenic mutations were identified in one multiplex family and one consanguineous family. Our study provided a useful piece of information for the genetic etiology of deafness in Uyghurs. © 2015 Chen et al.
Pang X.,Shanghai JiaoTong University |
Pang X.,Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases |
Pang X.,Peoples Hospital of Jiangsu Province |
Luo H.,Shanghai JiaoTong University |
And 14 more authors.
PLoS ONE | Year: 2015
Microdeletions in chromosome 17q22, where the NOG gene resides, have been reported leading to the NOG-related symphalangism spectrum disorder (NOG-SSD), intellectual disability and other developmental abnormalities. In this study we reported a dominant Chinese Han family segregating with typical NOG-SSD symptoms including proximal symphalangism, conductive hearing loss, amblyopia and strabismus, but not intellectual disability. Sanger sequencing identified no pathogenic mutation in the coding regions of candidate genes NOG, GDF5 and FGF9. SNP genotyping in the genomic region surrounding NOG identified loss of heterozygosity in the affected family members. By array comparative genomic hybridization and quantitative real-time polymerase chain reaction, we identified and mapped the breakpoints of a novel 1.6-Mb microdeletion in chromosome 17q22 that included NOG and twelve other genes. It is the first microdeletion reported in chromosome 17q22 that is associated with NOG-SSD only but not with intellectual disability. Our results may help identifying the dosage sensitive genes for intellectual disability and other developmental abnormalities in chromosome 17q22. Our study also suggested that genomic deletions in chromosome 17q22 should be screened in the NOG-SSD patients in which no pathogenic mutation is identified by conventional sequencing methods. Copyright: © 2015 Pang et al.
Zhu W.D.,Shanghai JiaoTong University |
Zhu W.D.,Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases |
Wang Z.Y.,Shanghai JiaoTong University |
Wang Z.Y.,Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases |
And 8 more authors.
European Journal of Medical Genetics | Year: 2015
The aim of this study was to assess the frequency of germline mutations and to explore genotype-phenotype associations in Chinese head and neck paraganglioma (HNPGL) patients without family history. Twenty-six Chinese patients with a diagnosis of HNPGL[U+FF08]14 male and 12 female, respectively[U+FF09]were recruited, who were followed up from 2000 to 2012. Genomic DNA was obtained from resected tumor tissues and peripheral blood samples. Seven genes, Succinate dehydrogenase complex A,B,C,D (SDHA, SDHB, SDHC, SDHD), succinate dehydrogenase complex assembly factor 2 (SDHAF2), TMEM127 (transmembrane protein 127) and VHL (Von Hippel-Lindau), were screened by direct sequencing and multiplex ligation-dependent probe amplification (MLPA) was performed to search for potential large deletions or duplications of SDHB, SDHC, SDHD, SDHAF1 and SDHAF2. The total frequency of germline mutations was 30.8% (8/26), including 5 cases with missense mutation p.Met1Ile in SDHD, 1 case with missense mutation p.Tyr216Cys in SDHB, and 1 case with a novel truncation mutation p.Gln44Ter in SDHAF2. MLPA showed one patient with malignant HNPGL had heterozygous deletions of exon1, 2, 3, 7 and 8 in SDHB. Mutations in SDHD were the leading cause of HNPGL in this study. Mutation carriers were younger than non-mutation carriers (. p < 0.01) and more likely to suffer from multiple tumors (. p = 0.048), especially with mutations in SDHD. The presence of mutation was associated with the development of larger tumors (. p = 0.021). This study confirmed that the missense mutation p.Met1Ile at the start codon in SDHD was a hotspot in chinese patients with HNPGLs. We recommend genetic analysis in patients below 45 years, especially SDHD gene. © 2015 Elsevier Masson SAS.
Yu Z.,Sun Yat Sen University |
Yu Z.,Shanghai JiaoTong University |
Yu Z.,Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases |
Wang Y.,Sun Yat Sen University |
And 12 more authors.
International Forum of Allergy and Rhinology | Year: 2015
Background: Oxidative stress is characteristic of chronic airway inflammatory diseases such as asthma, chronic obstructive pulmonary disease and chronic rhinosinusitis with nasal polyps (CRSwNP). Heme oxygenase (HO)-1 has been proposed to be a cytoprotective enzyme against oxidative stress in CRSwNP. However, the expression and regulation of HO-1 in eosinophilic CRSwNP (ECRS) and non-eosinophilic CRSwNP (non-ECRS) subsets has not been well documented. Methods: Nasal polyps and uncinate process tissues were enrolled from 40 CRSwNP patients (ECRS, 17; non-ECRS, 23) and 20 control subjects, respectively. The messenger RNA (mRNA) and protein expression of HO-1 was examined using qRT-PCR, immunohistochemistry, and Western blot staining. Moreover, the stimulatory effects of several cytokines (interferon γ [IFN-γ], interleukin [IL]-5, and IL-13, etc.) on HO-1 mRNA expression in cultured nasal explants were evaluated. Results: The mRNA and protein expression of HO-1 was significantly increased in polyp tissues compared with healthy controls (p < 0.05), and the non-ECRS subset showed significantly increased HO-1 expression compared with the ECRS subset (p < 0.05). Moreover, in cultured nasal explant, HO-1 mRNA was significantly upregulated in the presence of IFN-γ, IL-27, IL-5, IL-13, and IL-17A, but was significantly inhibited by transforming growth factor β1 (TGF-β1) (p < 0.05). Conclusion: Our findings indicate that HO-1 was differentially expressed and regulated in ECRS and non-ECRS patients. © 2015 ARS-AAOA, LLC.
Wu X.,Sun Yat Sen University |
Hong H.,Sun Yat Sen University |
Zuo K.,Sun Yat Sen University |
Zuo K.,Shenzhen University |
And 9 more authors.
International Forum of Allergy and Rhinology | Year: 2016
Background: Cysteinyl leukotriene (LT) has been proposed in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). This study sought to examine the expression of the LT receptor (LTR) in CRSwNP patients and evaluate the potential role of LTR antagonist (LTRA) in the management of eosinophilic CRSwNP (ECRS) patients. Methods: Nasal polyps and uncinate process tissues were collected from 18 ECRS patients, 13 non-eosinophilic CRSwNP (non-ECRS) patients, and 16 control subjects. The messenger RNA (mRNA) and protein expression of LTR (cysteinyl leukotriene receptor 1 [CysLT1R] and cysteinyl leukotriene receptor 2 [CysLT2R]) was examined using quantitative reverse-transcription polymerase chain reaction (qRT-PCR), immunohistochemistry, and Western blot analysis. Moreover, the effects of LTRA and steroids on total nasal symptom scores (TNSS) of uncontrolled ECRS patients were evaluated. Results: The mRNA and protein expression of CysLT1R and CysLT2R was significantly increased in polyp tissues compared with healthy controls (p < 0.05). Compared with the non-ECRS subset, the ECRS subset showed significantly increased expression of CysLT1R and CysLT2R, as well as leukotriene C4 (LTC4) and leukotriene D4 (LTC4) levels (p < 0.05). Moreover, combined LTRA and steroids significantly decreased TNSS more than steroids alone in uncontrolled ECRS patients (p < 0.01). Conclusion: Our findings indicate that LTR was differentially expressed between ECRS and non-ECRS patients, and that LTRA may be used as an additional therapy for ECRS patients. © 2016 ARS-AAOA, LLC.
Chen D.-Y.,Shanghai JiaoTong University |
Chen D.-Y.,Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases |
Zhu W.-D.,Shanghai JiaoTong University |
Zhu W.-D.,Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases |
And 10 more authors.
International Journal of Pediatric Otorhinolaryngology | Year: 2015
Objectives: Mutations in MT-TS1 have been found to be associated with nonsyndromic sensorineural hearing loss (SNHL). PCDH15 codes for protocadherin-15, a member of the cadherin superfamily of calcium-dependent cell-cell adhesion molecules. In this study, we analyzed the correlation of both MT-TS1 and PCDH15 mutations in a Chinese Han family segregating maternally inherited nonsyndromic SNHL. Methods: We ascertained a Chinese Han family segregating maternally inherited nonsyndromic sensorineural hearing loss. Eight of 10 maternal members in this family exhibited late-onset, progressive hearing impairment. Mutation screening of 79 known deafness genes was performed for the proband by targeted next-generation sequencing. Results: A total of 651 variants were detected in this individual. Among them, a homoplasmic 7511T>C variant in MT-TS1, the mitochondrial tRNA Ser(UCN) gene, and a heterozygous p.Asp1010Gly variant in PCDH15 were more likely to be pathogenic. Consistent with the matrilineal inheritance with reduced penetrance, the 7511T>C variant in MT-TS1 was found in all 10 maternal members and an additional heterozygous p.Asp1010Gly variant in PCDH15 cosegregated with the hearing loss in this family. Conclusion: Our results suggested that the PCDH15 p.Asp1010Gly variant probably modified the phenotypic expression of the 7511T>C mutation in MT-TS1. © 2015 Elsevier Ireland Ltd.