Exome sequencing identifies POU4F3 as the causative gene for a large Chinese family with non-syndromic hearing loss.

Hearing impairment, or deafness (in its most severe form), is one of the most common human sensory disorders. There have been several reports of autosomal dominant mutations in the POU4F3 gene, which is associated with non-syndromic hearing loss. In this study, we identified a novel heterozygous mutation (c.602delT, p.L201fs) in the gene POU4F3 by taking advantage of whole-exome sequencing, which was validated by Sanger sequencing and completely co-segregated within a large hearing impaired Chinese family. We have focused on this pedigree since 2002, and we have mapped a deafness locus named DFNA42 (which has been renamed DFNA52, OMIM entry 607683) via a genome-wide scan. Furthermore, we analyzed this mutational variant and found that it was located at the beginning of the first functional domain of POU4F3, which could theoretically impair the function of POU4F3. We have identified a novel frameshift mutation in the POU4F3 gene. Further functional studies of variants of this specific gene are needed to illustrate the pathogenic mechanism(s) that underlie hearing impairment.

iTRAQ-Based Quantitative Proteomic Analysis of Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is a common disease in the southern provinces of China with a poor prognosis. To better understand the pathogenesis of NPC and identify proteins involved in NPC carcinogenesis, we applied iTRAQ coupled with two-dimensional LC-MS/MS to compare the proteome profiles of NPC tissues and the adjacent non-tumor tissues. We identified 54 proteins with differential expression in NPC and the adjacent non-tumor tissues. The differentially expressed proteins were further determined by RT-PCR and Western blot analysis. In addition, the up-regulation of HSPB1, NPM1 and NCL were determined by immunohistochemistry using tissue microarray. Functionally, we found that siRNA mediated knockdown of NPM1 inhibited the migration and invasion of human NPC CNE1 cell line. In summary, this is the first study on proteome analysis of NPC tissues using an iTRAQ method, and we identified many new differentially expressed proteins which are potential targets for the diagnosis and therapy of NPC.

[Surgery of ventilation tube insertion in the middle ear and the external auditory canal for chronic secretory otitis media in children].

OBJECTIVE: To study the therapeutic effect of ventilation tube insertion in the middle ear and the external auditory canal on chronic secretory otitis media in children. METHODS: A retrospective study on 30 patients (40 ears) with chronic secretory otitis media and who underwent the operation of middle ear exploration and ventilation tube insertion in the middle ear and the external auditory canal was performed. Poor tympanic membrane, even with adhesion, was seen in 23 ears. Ten patients had evidence of bilateral secretory otitis media. From this group one ear was first injected with drugs (dexamethasone, mucosolvin, etc) and then tube insertion into the auditory tube was performed; the other ear only received drug injections into the auditory tube. The remaining 20 patients who had evidence of unilateral secretory otitis media only received drug injections into the auditory tube. RESULTS: The tubes inserting into the auditory tube all dropped out 5-8 days after operation. None of the ventilation tubes into the middle ear dropped out and the patients' tympanum recovered after the ventilation tubes were removed (6-8 months after operation). The total cure rate was 87.5% (35/40) and the improvement rate was 12.5% (5/40). The operation of inserting tubes into the auditorytube did not improve the therapeutic effects. In the 0.5-2 years postoperative follow-up, middle ear effusions recurred in one ear, and three ears were transferred from type C to type A. CONCLUSIONS: The surgery of ventilation tube insertion in the middle ear and the external auditory canal for chronic secretory otitis media can prevent the tympanic membrane from damage and dropping out of the ventilation tube and reduce recurrence in children. It is a preferred selection for the patients with poor tympanic membrane or adhesive tympanic membrane. It is no use to insert the tube into the auditory tube for the improvement of therapeutic effects.

[A preliminary study of endoscopic transoral trans-posteriorwall pharynx resection of hypo-clivus chordoma].

OBJECTIVE: To introduce a endoscopic surgical approach for hypo-clivus chordoma, and to explore the clinical value of the endoscopic resection of hypo-clivus chordoma. METHODS: Three hypo-clivus chordoma were resected by endoscopic transoral tans-posteriorwall pharynx approach. RESULTS: The MR image showed that total removal of the tumor was achieved in 2 patients and subtotal resection was received in one patient. No severe postoperative complications and sequelae occurred. In 6 months to 2 years' follow-up, the MRI showed that 2 patients had no residue tumor, and one patient died due to recurrence of the tumor 1 year after operation. CONCLUSION: The endoscopic transoral tans-posteriorwall pharynx approach might be valuable in the treatment of the hypo-clivus chordoma. The use of the endoscope allows for direct access to the hypo-clivus lesions while minimizing the chances of surrounding anatomic structure injury. In addition, this approach has the advantages of quick recovery, avoidance of catastrophic complications and sequelae. Especially, various angle view of the endoscope provides a panoramic view of the hypo-clivus, thus exposing and resecting hide lesion which can not be exposed by other approaches. This approach might facilitate complete resection of the chordoma with maximal preservation of normal tissues.