Fazil Apaydin

Substitutions in the conserved C2C domain of otoferlin cause DFNB9, a form of nonsyndromic autosomal recessive deafness.

DFNB, the nonsyndromic hearing loss with an autosomal recessive mode of inheritance constitutes the majority of severe to profound prelingual forms of hearing impairment, usually leading to inability of speech acquisition. We analyzed a consanguineous family with autosomal recessive deafness which has been shown to segregate within chromosomal region 2p23.1 (DFNB9; MIM 601071). By SSCP analysis and DNA sequencing of the 48 exons of the DFNB9 gene, coding for otoferlin, previously reported mutations in OTOF were excluded. Next to a frequent T > C single nucleotide polymorphism in exon 8, two novel mutations linked in exon 15 of the OTOF long splice form were identified comprising substitutions at positions 490 (Pro > Gln) and 515 (Ile > Thr), both located in the conserved Ca(2+) binding C2C domain of this peptide. Comparisons of homology using human and mice otoferlins and closely related peptides and computer simulation analyses suggest that changes in the mutated segments secondary structure affect the Ca(2+) binding capacity of the C2C domain in otoferlin.

A Genotype-Phenotype Correlation with Gender-Effect for Hearing Impairment Caused by TECTA Mutations

Background: Alpha-tectorin is a noncollagenous component of the tectorial membrane which plays an essential role in auditory transduction. In several DFNA12 families mutations in TECTA, the gene encoding alpha-tectorin, were shown to cause hearing impairment (HI) with different phenotypes depending on the location of the mutation. Methods/Results: Here we report a Turkish family displaying autosomal dominant inherited HI. Linkage analysis revealed significant cosegregation (LOD score: 4.6) of the disease to markers on chromosome 11q23.3- q24. This region contains the TECTA gene which was subsequently sequenced. A nucleotide change in exon 13, 4526T>G, was detected leading to a substitution from cysteine to glycine at codon 1509 of the TECTA protein. This cysteine is located in vWFD4 domain, a protein domain which is supposed to be involved in disulfide bonds and protein-protein interactions. Conclusions: It is conspicuous that the phenotype in this family correlates with other families, also displaying mutations involving conserved cysteines. In all three families these mutations result in progressive HI involving high frequencies. In contrast, mutations which are not affecting the vWFD domains seem to provoke mid-frequency sensorineural HI. Furthermore, evaluation of clinical data in our family revealed a gender effect for the severity of hearing impairment. Males were significantly more affected than females. The identification of the third family displaying a missense mutation in the vWFD domain of alpha- tectorin underlines the phenotype-genotype correlation based on different mutations in TECTA.

Nasal Valve Surgery

Nasal obstruction can be due to internal and external valve problems that can be seen before and after rhinoplasty. The main scope of this article is to concentrate on surgical solutions to these problems. To overcome nasal obstruction at the internal valve, spreader grafts, spreader flaps, upper lateral splay graft, butterfly graft, flaring suture, M-plasty, Z-plasty, and suspension sutures have been described. The management of the external valve problems is possible by using lateral crural dissection and repositioning, lateral crural strut grafts, alar battens, lateral crural turn-in flap, alar rim grafts, and various other methods. It is not easy to decide which techniques would work best in every case. After a thorough examination and analysis, the underlying cause of the nasal obstruction can be understood, and one or multiple procedures can be chosen according to each individual problem.

Rhinobase: A Comprehensive Database, Facial Analysis, and Picture-Archiving Software for Rhinoplasty

Correspondence: Dr Hamilton, Department of Otolaryngology–Head and Neck Surgery, Division of Facial Plastic and Reconstructive Surgery, University of Iowa Hospitals and Clinics, 200 Hawkins Dr, Iowa City, IA 52242 (grant-hamilton@uiowa.edu). Financial Disclosure: None reported. Additional Contributions: Norman Koren, MA, of Imatest provided his insights on camera testing and image analysis, and M. Bridget Zimmerman, PhD, provided statistical consultation.

Clinical evidence for dystrophin dysfunction as a cause of hearing loss in locus DFN4.

Objective: Locus DFN4 is an X‐linked nonsyndromic hearing loss locus originally mapped to Xp21.2. Recently, we have mapped deafness in a second family from Turkey to the same region, refining the location to within the Duchenne muscular dystrophy (DMD) locus. The objective of this study was to characterize the clinical phenotype of the Turkish family with comprehensive audiovestibular testing and high‐resolution temporal bone computerized tomography. Methods: Fourteen members of a three‐generation family were studied in detail including two deaf affected males. Members of the family underwent general physical and otologic examination, vestibular testing, pure‐tone audiometry, otoacoustic emissions, and immitance testing. An affected male underwent high‐resolution computerized tomography of the temporal bone, electroretinogram (ERG), electromyography, electroneurography, and determination of serum creatinine phosphokinase level. Results: Affected males were congenitally deaf with normal vestibular function. Carrier females showed a mild sensorineural hearing loss affecting all frequencies and absent otoacoustic emissions. Otoacoustic emissions in a younger, 3‐year‐old carrier girl were normal. In an affected male, ERG demonstrated subnormal scotopic b‐wave typically seen in DMD. Computerized tomography of the temporal bone was normal. With the exception of the ERG finding, there was no clinical or laboratory evidence of DMD or Becker muscular dystrophy (BMD). Conclusion: The abnormal ERG in the Turkish family in conjunction with mapping of the DFN4 locus to within DMD strongly suggests that a defect in dystrophin is responsible for the hearing loss in this family. Patients with DMD and BMD should be screened systematically for sensorineural hearing loss. This family provides additional evidence for the critical role of cytoskeletal proteins in normal hearing.

A second middle eastern kindred with autosomal recessive non-syndromic hearing loss segregates DFNB9.

A second kindred has been identified which supports the previously reported location of DFNB9. Linkage has been established to markers closely linked to DFNB9 which is located on 2p22-p23. The hearing impaired individuals in this highly consanguineous kindred from Eastern Turkey have prelingual profound hearing loss which affects all frequencies. A genetic map of the 2p22-p23 region where DFNB9 resides was generated using marker genotypes available from the CEPH database. All markers were placed on this genetic map using a likelihood ratio criterion of 1000:1. This map suggests that the region for DFNB9 is less than 1.08 cM, 95% confidence interval (0–2.59 cM).

Long-term Follow-up of Positive Surgical Margins in Basal Cell Carcinoma of the Face.

BACKGROUND Basal cell carcinoma (BCC) in central facial locations and tumors with positive margins are at a higher risk of recurrence. The most effective treatment is total excision, which includes an adequate pathological margin. OBJECTIVE To evaluate the outcome of the patients who underwent surgery for BCCs of the head and neck and of those who had positive surgical margins where Mohs surgery is not available. METHODS This study was conducted at Ege University Medical School between 2004 and 2014. One hundred thirty patients with 154 BCC who underwent surgical excision were included. In the histopathologic report, the existence of positive margin, BCC subtype, localization of the tumor, and distance of margins to the tumor were evaluated. RESULTS Twenty-three lesions (14.9%) of 22 patients revealed positive surgical margins. Six patients (26.1%) had recurrences on the surgical site. The BCC subtypes of recurrent patients were reported to be multifocal superficial in 2 (33.3%), infiltrative (16.7%) in 1, and micronodular (50%) in 3. CONCLUSION Patients with superficial multifocal or micronodular tumors should undergo reoperation because of high recurrence rates.

Bone recycling in nasal septal reconstruction.

Septal reconstruction alone or together with rhinoplasty can be a very challenging operation. In situations where septal cartilage is used for grafting or is not enough, bony implants taken from the perpendicular plate of the ethmoid and vomer can be used as a filler material between the mucoperichondrial flaps to avoid from unwanted mucosal atrophy, flapping, and septal perforation. These bony implants can also be used for splinting the dorsal and/or caudal segment of the septal cartilage after reshaping by rongeurs. On rare occasions, they can even be used for subtotal reconstruction of the septum.

Rebuilding the Middle Vault in Rhinoplasty: A New Classification of Spreader Flaps/Grafts

After hump removal in reduction rhinoplasty, one of the main steps is to rebuild the middle vault. Spreader grafts have long been the main tool for the surgeon. Within the last two decades, the spreader flaps have started to be very popular as well. In accordance with the experience and technical preferences of the surgeon, there are many different options. In this article, the spreader grafts are classified as traditional, modified, splinting, and reconstructive. The spreader flaps are designed in accordance with their relationship with the septum and the spreader grafts.

Projection and Deprojection Techniques in Rhinoplasty

Projection of the nasal tip is among the most important aspects of the nose. In this article, a wide spectrum of techniques are presented that allow the rhinoplasty surgeon to decrease, maintain, or increase nasal tip projection. Rhinoplasty surgeons must be adept with suture techniques, lower lateral cartilage overlay techniques, and structural grafting to be able to achieve excellent long-term results.