Publications by authors named "Armagan Incesulu"

46 Publications

Perception of male otolaryngologists on gender discrimination: a comparative study.

Eur Arch Otorhinolaryngol 2020 Sep 17. Epub 2020 Sep 17.

Otolaryngology Head and Neck Surgery, Denizli Pamukkale University Medical Faculty, Denizli, Turkey.

Purpose: To gather information on perception of male otolaryngologists (MORLs) about gender discrimination towards female otolaryngologists (FORLs).

Methods: MORLs were invited to participate to an online survey. Minimum participation requirement was completion of at least their first year of residency. The responses were analyzed and compared vis-a-vis with the previously conducted similar survey among FORLs.

Results: Statistically significant responses on the Likert scale are classified in four main groups. MORLs and FORLs share the same views about financial factors, benefits and opportunities, housework as burden, establishing work-life balance and physical strength requirements. They have opposing views about FORLs being meticulous, exposed to more negative attitude of the opposite gender and men's dominance in decision-making. FORLs don't have consensus, but MORLs disagree about MORLs being favored in pursuing academic careers. On the other hand, MORLs don't have consensus, but FORLs agree about patients having more confidence in MORLs.

Conclusion: MORLs don't usually have any confrontation with FORLs in regards to the roles of women in the society such as their motherhood role. On the other hand, MORLs show rather a contradiction on their perception towards the gender discrimination mainly in achieving career goals by FORLs such as growing in the profession and holding managing roles. When the views of the both gender group are compared, MORLs don't seem to fully acknowledge FORLs' gender discrimination experience.
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http://dx.doi.org/10.1007/s00405-020-06354-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497857PMC
September 2020

Association Between Incomplete Partition Type III and Abnormal Hypothalamic Morphology: Further Imaging Evidence.

J Comput Assist Tomogr 2020 Sep/Oct;44(5):704-707

Department of Otorhinolaryngology, Faculty of Medicine, Eskisehir Osmangazi University, Meselik-Eskisehir, Turkey.

Purpose: Incomplete partition III (IP-III), characterized by congenital mixed or sensorineural hearing loss, is a rare genetic disease transmitted through X-linked mode of inheritance. Inner ear findings of IP-III have been well described and allow an immediate diagnosis to be made. Recently, an association between IP-III and distinct hypothalamic malformations has been reported in some of the patients with IP-III. The purpose of this study was to investigate the morphologic abnormalities of the hypothalamus in IP-III.

Materials And Methods: Magnetic resonance imaging studies of 8 subjects, including 1 set of brothers, who were diagnosed with IP-III based on their clinical and inner ear imaging findings, were analyzed.

Results: Of the 8 subjects, 7 demonstrated some degree of morphologic abnormality of the hypothalamus. Of these, 2 showed asymmetrical thickening, 1 showed symmetrical thickening, and 4 showed mass-like enlargement of the hypothalamus. Six of 7 subjects with hypothalamic abnormalities showed asymmetry in caudal extension of the abnormalities, which was more discernible on coronal oblique T2-weighted images. Clinically, none of the subjects had endocrinologic or neurologic symptoms.

Conclusions: This retrospective analysis presents further magnetic resonance imaging evidence on the association between the rare IP-III malformations and the presence of hypothalamic morphologic abnormalities.
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http://dx.doi.org/10.1097/RCT.0000000000001050DOI Listing
September 2020

Analysis of cochlear implant revision surgeries.

Eur Arch Otorhinolaryngol 2021 Mar 15;278(3):675-682. Epub 2020 Jun 15.

Department of Otorhinolaryngology - Head and Neck Surgery, School of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.

Purpose: This study aimed to evaluate the reasons for cochlear implant (CI) revision surgeries in pediatric and adult groups.

Methods: A total of 490 CIs were used for 423 patients between August 2005 and August 2019. Among these, patients who underwent a CI revision surgery were identified retrospectively. The reasons for CI revision surgeries were classified mainly as medical problems and device failure. These were also determined according to implant brands.

Results: Of 423 patients with a CI surgery, 27 (6.3%) underwent a CI revision surgery. The revision implant rate was 4.9% for the pediatric group and 1.4% for the adult group. Five patients underwent a CI revision surgery due to medical problems (23.8%) and 16 due to device failure (76.2%) in the pediatric group, while 3 patients (50.0%) underwent a CI revision surgery due to medical problems and 3 (50.0%) due to device failure in adults.

Conclusions: A CI surgery is safe for patients with severe-to-profound sensorineural hearing loss, although a CI revision surgery has some potential. Device failure is the most common cause in children. It may be due to early implantation, frequent fall when children learn walking, or impaired vestibular function.
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http://dx.doi.org/10.1007/s00405-020-06121-5DOI Listing
March 2021

Long-range cis-regulatory elements controlling GDF6 expression are essential for ear development.

J Clin Invest 2020 08;130(8):4213-4217

John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.

Molecular mechanisms governing the development of the mammalian cochlea, the hearing organ, remain largely unknown. Through genome sequencing in 3 subjects from 2 families with nonsyndromic cochlear aplasia, we identified homozygous 221-kb and 338-kb deletions in a noncoding region on chromosome 8 with an approximately 200-kb overlapping section. Genomic location of the overlapping deleted region started from approximately 350 kb downstream of GDF6, which codes for growth and differentiation factor 6. Otic lineage cells differentiated from induced pluripotent stem cells derived from an affected individual showed reduced expression of GDF6 compared with control cells. Knockout of Gdf6 in a mouse model resulted in cochlear aplasia, closely resembling the human phenotype. We conclude that GDF6 plays a necessary role in early cochlear development controlled by cis-regulatory elements located within an approximately 500-kb region of the genome in humans and that its disruption leads to deafness due to cochlear aplasia.
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http://dx.doi.org/10.1172/JCI136951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410044PMC
August 2020

Irregular Contour of Inner Ear Structures and Hypomineralized Areas at Otic Capsule: Are They Other Additional Imaging Findings of Incomplete Partition-III?

J Comput Assist Tomogr 2020 May/Jun;44(3):386-388

Otorhinolaryngology, Eskisehir Osmangazi University, Faculty of Medicine, Eskisehir, Turkey.

Purpose: Incomplete partition III (IP-III) characterized by congenital mixed or sensorineural hearing loss is a rare genetic disease transmitted through X-linked inheritance. Incomplete partition III can be easily achieved based on pathognomonic computed tomography findings. The aims of this study were to investigate the otic capsule abnormalities in IP-III and to report irregular contour of membranous labyrinth and hypomineralized areas at otic capsule, which have not previously been described.

Materials And Methods: The otic capsule features of 10 subjects (8 affected patients, 1 of whom is a female; 2 carrier mothers), who were diagnosed on clinical and typical radiologic findings, were analyzed.

Results: All patients had typical IP-III as described in the literature. Seven of 10 patients had irregular contour. Seven of 10 patients demonstrated hypomineralized areas, which were very hypodense to normally develop otic capsule areas. One affected patients and 2 carrier mothers had a normal-looking membranous labyrinth contour and normal mineralization at otic capsule.

Conclusions: We report for the first time the irregular contour of inner ear structures and hypodense otic capsule areas in patients with IP-III. We think that though speculative, abnormal development of the inner endosteal layer results in irregular contour of inner ear structures. Hypomineralized areas at otic capsule could be explained by abnormal development of middle enchondral layer due to reduced or absent vascular supply from middle ear mucosa during fetal life. These findings may be accepted as additional criteria of IP-III.
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http://dx.doi.org/10.1097/RCT.0000000000000991DOI Listing
May 2020

Women in otolaryngology in Turkey: Insight of gender equality, career development and work-life balance.

Am J Otolaryngol 2020 Jan - Feb;41(1):102305. Epub 2019 Oct 18.

Akdeniz University, School of Medicine, Department of Medical Education, Turkey.

Objective: The aim of this study is to collect information about the demographics, academic ambitions, job satisfactions, career development and work-life balance of female otorhinolaryngologists (FORL) in Turkey and to determine their experiences with, and attitudes towards gender discrimination throughout their academic careers.

Study Design And Setting: A prospective survey study.

Subjects And Methods: The study was aimed to include all FORL who completed their residency program. An online survey was used to collect their responses.

Results: Out of 208 invitations, 156 FORL participated to the survey. The mean age of the participants was 39.7 ± 6.1 (29-75) years. 16.6% of the FORL used to occupy or still occupying administrative positions in their respective medical centers; 15.4% of them used to be assigned or still being assigned to a duty in otorhinolaryngology associations. Gender discrimination was 2.5 fold higher (p = 0.006 OR: 2.55 (95% CI 1.31, 4.99) in departments where there were no female faculty members. 53.2% of the female surgeons were both physically and psychologically harassed for their gender during their residency programs to deter from completing their program in otolaryngology. This finding is 4.1 fold higher than those who stated that they had not been exposed to any such gender discrimination (p = 0.001 OR: 4.094 (95% CI 2.22, 7.57).

Conclusion: Healthcare policy-makers and institutions should consider taking all the necessary actions to prevent gender discrimination in order to increase job satisfaction and achievements of female specialists in the field of otorhinolaryngology.
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http://dx.doi.org/10.1016/j.amjoto.2019.102305DOI Listing
April 2020

The Effectiveness of Medical Prophylactic Treatment on Vestibular Migraine and Its Effect on the Quality Of Life.

J Int Adv Otol 2020 Apr;16(1):28-33

Clinic of Otorhinolaryngology, Ağrı Diyadin State Hospital, Ağrı, Turkey.

Objectives: The aim of the present study was to determine the efficacy of propranolol treatment in patients with vestibular migraine by the Visual Analog Scale, Dizziness Handicap Inventory (DHI), Vertigo Symptom Scale, and Vestibular Disorders Activities of Daily Living Scale (VADL) and its effect on the quality of life.

Materials And Methods: The study population consisted of 38 patients with vertigo/dizziness who underwent routine evaluation and vestibular examinations, were diagnosed with definitive vestibular migraine, and received the same medical treatment protocol (propranolol). The questionnaires and scales that were applied to the patients before and after treatment were evaluated. The results were evaluated with 95% confidence interval, and p<0.05 was accepted as statistically significant.

Results: The mean age of the patients was 47.55 (18-75) years, and 27 (71%) patients were female, and 11 (29%) were male. The mean total scores of the DHI before and after treatment were 50.21±22.39 (range: 8-92) and 9.31±9.86 (range: 0-58), respectively (p<0.001). The degree of disability after treatment was low in all patients (p<0.001). The total scores of the VADL before and after treatment were 186.63±79.65 (range: 32-280) and 55.52±51.89 (range: 28-273), respectively (p<0.001). There was no correlation between these two scales (p=0.235).

Conclusion: To our knowledge, this is the first study to evaluate both the efficacy of propranolol treatment and its effects on the quality of life in vestibular migraine. The severity, frequency, and number of attacks and disability scores were reduced, and the quality of life was improved in patients with vestibular migraine with propranolol treatment.
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http://dx.doi.org/10.5152/iao.2019.6522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224423PMC
April 2020

FOXF2 is required for cochlear development in humans and mice.

Hum Mol Genet 2019 04;28(8):1286-1297

John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.

Molecular mechanisms governing the development of the human cochlea remain largely unknown. Through genome sequencing, we identified a homozygous FOXF2 variant c.325A>T (p.I109F) in a child with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is not found in public databases or in over 1000 ethnicity-matched control individuals. I109 is a highly conserved residue in the forkhead box (Fox) domain of FOXF2, a member of the Fox protein family of transcription factors that regulate the expression of genes involved in embryogenic development as well as adult life. Our in vitro studies show that the half-life of mutant FOXF2 is reduced compared to that of wild type. Foxf2 is expressed in the cochlea of developing and adult mice. The mouse knockout of Foxf2 shows shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Expressions of Eya1 and Pax3, genes essential for cochlear development, are reduced in the cochleae of Foxf2 knockout mice. We conclude that FOXF2 plays a major role in cochlear development and its dysfunction leads to SNHL and developmental anomalies of the cochlea in humans and mice.
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http://dx.doi.org/10.1093/hmg/ddy431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452198PMC
April 2019

International Otology Outcome Group and the International Consensus on the Categorization of Tympanomastoid Surgery.

J Int Adv Otol 2018 Aug;14(2):216-226

Department of Otolaryngology-Head and Neck Surgery, Eskişehir Osmangazi University Faculty of Medicine, Eskişehir, Turkey.

The International Otology Outcome Group (IOOG) was founded in 2017 to encourage and facilitate international collaboration with regard to the surgical outcome of ear surgery. This report outlines the methodology and recommendations of the consensus-based categorization of tympanomastoid surgery produced by the IOOG. The IOOG Steering Committee used the acronym SAMEO-ATO to categorize tympanomastoid operations, representing the stage of surgery, approach, mastoid bone extirpation, external bony wall repair, obliteration of the mastoid cavity, access to the middle ear, tympanic membrane reconstruction, and ossicular reconstruction. A modified Delphi technique was used to obtain international consensus. The expert panels included the chairpersons from 21 otology societies. The approval rate of the SAMEO-ATO system from the otology societies was 95%. The SAMEO-ATO scheme was presented at the 31st Politizer Meeting for field testing. There were no objections or serious concerns raised. Some international otologists wished to see more surgical categories included to reflect the varieties of surgical techniques, but they accepted that it would make the whole system cumbersome. In addition to providing an international categorization of tympanomastoid surgery, the IOOG Steering Committee plans to introduce a common otology dataset that the international otology community could use to record their surgical outcome. The high level of international consensus on the IOOG categorization of tympanomastoid surgery supports this tool for surgeons to pool their surgical data into a large database for research and comparative audit.
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http://dx.doi.org/10.5152/iao.2018.5553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354466PMC
August 2018

MPZL2 is a novel gene associated with autosomal recessive nonsyndromic moderate hearing loss.

Hum Genet 2018 Jul 7;137(6-7):479-486. Epub 2018 Jul 7.

John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA.

While recent studies have revealed a substantial portion of the genes underlying human hearing loss, the extensive genetic landscape has not been completely explored. Here, we report a loss-of-function variant (c.72delA) in MPZL2 in three unrelated multiplex families from Turkey and Iran with autosomal recessive nonsyndromic hearing loss. The variant co-segregates with moderate sensorineural hearing loss in all three families. We show a shared haplotype flanking the variant in our families implicating a single founder. While rare in other populations, the allele frequency of the variant is ~ 0.004 in Ashkenazi Jews, suggesting that it may be an important cause of moderate hearing loss in that population. We show that Mpzl2 is expressed in mouse inner ear, and the protein localizes in the auditory inner and outer hair cells, with an asymmetric subcellular localization. We thus present MPZL2 as a novel gene associated with sensorineural hearing loss.
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http://dx.doi.org/10.1007/s00439-018-1901-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478175PMC
July 2018

Efficacy of Platelet-Rich Plasma on Fat Grafts in the Repair of Tympanic Membrane Perforations: An Experimental Study.

J Int Adv Otol 2018 Apr 14;14(1):58-62. Epub 2017 Dec 14.

Department of Ear Nose and Throat, Eskişehir Osmangazi University School of Medicine, Eskişehir, Turkey.

Objective: We investigated the use of autologous platelet-rich plasma (PRP) to improve the success rate of fat graft myringoplasty in perforated tympanic membranes of rats.

Materials And Methods: A total of 20 healthy Wistar albino female rats were divided into two groups. In Group 1, the left tympanic membranes were perforated and grafted with a fat graft that was harvested from the inguinal region. In Group 2, the left tympanic membranes were perforated, and a fat graft was also harvested from the inguinal region. Then, the fat was soaked in 0.5 mL PRP and grafted at the perforation. After the procedure, the rats were examined, and the graft situation was assessed at 3, 5, 7, 10, and 14 days. All of the rats were sacrificed 21 days after perforation, and a histopathological examination was made.

Results: We compared fat graft histopathological and otomicroscopic findings between the groups. While we did not observe graft rejections in Group 2, we saw 1 case of graft rejection in Group 1. In the histopathological examination, PRP prevents fat graft resorption by the terms of the adipocyte area, granulation tissue area, and vacuolization area.

Conclusion: This study demonstrated the efficacy of fat grafts prepared with PRP on rat tympanic membranes. The fat graft with PRP did not statistically improve the success rate compared to the graft without PRP. Histopatologic findings of the study showed that PRP prevents fat graft resorption. Further studies are needed to further examine the advantages of the graft with PRP.
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http://dx.doi.org/10.5152/iao.2017.3845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354494PMC
April 2018

Cochlear Implantation in Patients with Keratitis-Ichthyosis-Deafness Syndrome: A Report of Two Cases.

Case Rep Otolaryngol 2017 2;2017:3913187. Epub 2017 Oct 2.

Department of Otorhinolaryngology, Faculty of Medicine, Eskişehir Osmangazi University, Eskişehir, Turkey.

Background: Keratitis-ichthyosis-deafness (KID) syndrome is a syndrome which presents with hearing loss and visual and keratinization disorders. In such patients, hearing aids cannot be effectively used in the rehabilitation of hearing loss because of the frequent blockage of the external ear canal with epithelial debris and due to dry and tense skin of the external ear canal. Moreover, severe or profound hearing loss also limits the benefits gained from the conventional hearing aids. On the other hand, cochlear implantation is a method that has been used in limited cases in the literature.

Case Report: This study presents the results of cochlear implantation applied in our clinic to two children who had been diagnosed with KID. Audiological assessments before and after the cochlear implant operation were performed using pure-tone audiometry, immittance audiometry, and auditory brainstem response (ABR), and the postoperative follow-up was conducted using pure-tone audiometry.

Conclusion: Skin problems, visual disturbances, and other additional problems complicate the short-term and long-term rehabilitation after implantation in individuals with KID syndrome. Close monitoring should be exercised due to possible skin complications that may develop during the postoperative period. The families and rehabilitation teams should be warned about the possible visual disturbances and skin complications.
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http://dx.doi.org/10.1155/2017/3913187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642881PMC
October 2017

Novel pathogenic variants underlie SLC26A4-related hearing loss in a multiethnic cohort.

Int J Pediatr Otorhinolaryngol 2017 Oct 8;101:167-171. Epub 2017 Aug 8.

John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, FL, USA; Dr. John T. Macdonald Foundation, Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL, USA; Department of Otorhinolaryngology, University of Miami, Miller School of Medicine, Miami, FL, USA. Electronic address:

Objectives: The genetics of sensorineural hearing loss is characterized by a high degree of heterogeneity. Despite this heterogeneity, DNA variants found within SLC26A4 have been reported to be the second most common contributor after those of GJB2 in many populations.

Methods: Whole exome sequencing and/or Sanger sequencing of SLC26A4 in 117 individuals with sensorineural hearing loss with or without inner ear anomalies but not with goiter from Turkey, Iran, and Mexico were performed.

Results: We identified 27 unique SLC26A4 variants in 31 probands. The variants c.1673A > G (p.N558S), c.1708-1G > A, c.1952C > T (p.P651L), and c.2090-1G > A have not been previously reported. The p.N558S variant was detected in two unrelated Mexican families.

Conclusion: A range of SLC26A4 variants without a common recurrent mutation underlies SLC26A4-related hearing loss in Turkey, Iran, and Mexico.
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http://dx.doi.org/10.1016/j.ijporl.2017.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679420PMC
October 2017

EAONO/JOS Joint Consensus Statements on the Definitions, Classification and Staging of Middle Ear Cholesteatoma.

J Int Adv Otol 2017 Apr 6;13(1):1-8. Epub 2017 Jan 6.

The Ipswich Hospital NHS Trust, Heath Road, Suffolk, United Kingdom IP4 5PD.

The European Academy of Otology and Neurotology (EAONO) has previously published a consensus document on the definitions and classification of cholesteatoma. It was based on the Delphi consensus methodology involving the broad EAONO membership. At the same time, the Japanese Otological Society (JOS) had been working independently on the "Classification and Staging of Cholesteatoma." EAONO and JOS then decided to collaborate and produce a joint consensus document. The EAONO/JOS joint consensus on "Definitions, Classification and Staging of Middle Ear Cholesteatoma" was formally presented at the 10th International Conference on Cholesteatoma and Ear Surgery in Edinburgh, June 5-8, 2016. The international otology community who attended the consensus session was given the chance to debate and give their support or disapproval. The statements on the "Definitions of Cholesteatoma" received 89% approval. The "Classification of Cholesteatoma" received almost universal approval (98%). The "EAONO/JOS Staging System on Middle Ear Cholesteatoma" had a majority of approval (75%). Some international otologists wanted to see more prognostic factors being incorporated in the staging system. In response to this, the EAONO/JOS steering group plans to set up an "International Otology Outcome Working Group" to work on a minimum common otology data set that the international otology community can use to evaluate their surgical outcome. This will generate a large database and help identify relevant prognostic factors that can be incorporated into the staging system in future revisions.
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http://dx.doi.org/10.5152/iao.2017.3363DOI Listing
April 2017

The Effect of Nasal Obstruction after Different Nasal Surgeries Using Acoustic Rhinometry and Nasal Obstruction Symptom Evaluation Scale.

World J Plast Surg 2016 Sep;5(3):236-243

Department of Otorhinolaryngology, Faculty of Medicine, Eskişehir Osmangazi University, Eskisehir, Turkey.

Background: The efficiency of nasal surgeries can be determined by objective or subjective methods. We have assessed the effect of nasal obstruction after different nasal surgeries using Acoustic Rhinometry (AR) and Nasal Obstruction Symptom Evaluation (NOSE) Scale.

Methods: Between May 2011 and May 2012, 40 young adult patients and 10 healthy volunteers as control group who referred to Otorhinolaryngology Clinic in Eskisehir Military Hospital due to nasal obstruction were enrolled. Depending on operation, patients were divided into four equal groups. Group 1: Septoplasty, Group 2: Septoplasty with sprader graft, Group 3: Septorinoplasty and Group 4: Septorhinoplasty with spreader graft. The patients completed NOSE scale, 1 week before and 1 month after the surgery and AR measurements.

Results: There were a significant improvement in mean NOSE scores of patients and statistical difference was found between pre and post-operational values for each group. There was a statistically significant change of the mean minimal cross section areas (MCA) of the deviated side of nasal passages measured by AR between pre and postoperative period.

Conclusion: In patients with nasal obstruction, functional nasal surgeries which were performed after appropriate medical examination and with right operation methods had a positive impact on quality of life and patient satisfaction. We observed that nasal findings were correlated with NOSE scores and MCA values. So, we suggest that NOSE scale and AR to be used for evaluation of the efficiency of functional nasal surgeries.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109384PMC
September 2016

Evaluation of the Vestibular System and Etiology in Children with Unilateral Sensorineural Hearing Loss.

J Int Adv Otol 2016 Aug;12(2):161-165

Department of Otorhinolaryngology, Yunus Emre State Hospital, Eskişehir, Turkey.

Objective: The aim of this study was to evaluate the vestibular system of children with unilateral sensorineural hearing loss (USNHL), investigate the etiological factors of USNHL and analyze whether a genetic predisposition exists.

Materials And Methods: Thirty-three children aged less than 18 years with USNHL, who visited the ear, nose, and throat (ENT) department between January 2004 and December 2012, were included in this study. Cases with conductive hearing loss were excluded from the study. The patients were subjected to etiologic, genetic, and ophthalmologic evaluation; radiologic imaging; electronystagmography (ENG); and vestibular evoked myogenic potential (VEMP) tests. The control group, which included 25 healthy children (13 males and 12 females), had undergone audiological assessment and were subjected to ENG and VEMP tests.

Results: All of the patients had severe-to-profound hearing loss. Mumps immunoglobulin G was positive in 22 (66.7%) of 33 patients. The 35delG mutation was not found in any of the patients. All of the patients underwent temporal computed tomography (CT) and magnetic resonance imaging (MRI). Inner ear anomaly was present in 51.5% of the patients. Overall, 21 of 31 ENG patients had canal paresis in the affected ear. The VEMP response was absent on the affected side in three patients. The n23 latency average of the patient group was longer than that of the control group.

Conclusion: Because USNHL causes irreversible problems in children, early diagnosis and auditory rehabilitation are very important. As USNHL is accompanied by inner ear anomaly, children with USNHL should undergo temporal bone CT and MRI. To evaluate the vestibular system, ENG and VEMP are non-invasive and diagnostic tests.
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http://dx.doi.org/10.5152/iao.2016.2439DOI Listing
August 2016

Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort.

Genet Med 2016 Apr 30;18(4):364-71. Epub 2015 Jul 30.

Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.

Purpose: Autosomal recessive nonsyndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity, with reported mutations in 58 different genes. This study was designed to detect deafness-causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES).

Methods: After excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador, and Puerto Rico to screen for mutations in all known ARNSD genes.

Results: We detected ARNSD-causing variants in 90 (56%) families, 54% of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13%), MYO7A (11%), SLC26A4 (10%), TMPRSS3 (9%), TMC1 (8%), ILDR1 (6%), and CDH23 (4%). Nine mutations were detected in multiple families with shared haplotypes, suggesting founder effects.

Conclusion: We report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56% of the families. In the remaining families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.Genet Med 18 4, 364-371.
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http://dx.doi.org/10.1038/gim.2015.89DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733433PMC
April 2016

Novel domain-specific POU3F4 mutations are associated with X-linked deafness: examples from different populations.

BMC Med Genet 2015 Feb 25;16. Epub 2015 Feb 25.

John P. Hussmann Institute for Human Genomics and John T. Macdonald Foundation, Department of Human Genetics, Miller school of Medicine, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA.

Background: Mutations in the POU3F4 gene cause X-linked deafness type 3 (DFN3), which is characterized by inner ear anomalies.

Methods: Three Turkish, one Ecuadorian, and one Nigerian families were included based on either inner ear anomalies detected in probands or X-linked family histories. Exome sequencing and/or Sanger sequencing were performed in order to identify the causative DNA variants in these families.

Results: Four novel, c.707A>C (p.(Glu236Ala)), c.772delG (p.(Glu258ArgfsX30)), c.902C>T (p.(Pro301Leu)), c.987T>C (p.(Ile308Thr)), and one previously reported mutation c.346delG (p.(Ala116ProfsX26)) in POU3F4, were identified. All mutations identified are predicted to affect the POU-specific or POU homeo domains of the protein and co-segregated with deafness in all families.

Conclusions: Expanding the spectrum of POU3F4 mutations in different populations along with their associated phenotypes provides better understanding of their clinical importance and will be helpful in clinical evaluation and counseling of the affected individuals.
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http://dx.doi.org/10.1186/s12881-015-0149-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422282PMC
February 2015

The round window diameter in congenital aural atresia and comparison with sensorineural hearing loss and control group.

J Comput Assist Tomogr 2014 May-Jun;38(3):461-3

From the *Departments of Radiology and †Otorhinolaryngology, Faculty of Medicine, Eskisehir Osmangazi University, Meselik-Eskisehir, Turkey.

Objective: The aim of this study was to measure round window (RW) diameters in patients with congenital aural atresia (CAA) or sensorineural hearing loss (SNHL) and a normal control group and to analyze whether differences exist between these groups.

Methods: Temporal bone computed tomographic scans of 12 patients with CAA (5 males, 7 females) aged 1 to 50 years (median age, 6 years), 12 patients with SNHL (8 males, 4 females) aged 2 to 32 years (median age, 5 years), and 11 patients (3 males, 7 females) aged 2 months to 53 years (median age, 8 years) randomly selected from a pool of patients with unilateral chronic otitis media or cholesteatoma were reviewed. We measured RW diameter on oblique reconstruction planes. To prevent possible individual differences, skull width was measured.

Results: There were no statistically significant differences between all groups for skull width. Both RW diameter and RW membrane width were found smaller in the CAA group than both SNHL group and control group with statistical significance, whereas there were no statistically significant differences between the SNHL group and the control group.

Conclusions: We found that both the RW diameter and RW membrane width in CAA were smaller than those in the control group. If this finding is supported in future studies, the production of floating mass transducer with different sizes may be useful. We suggest that RW diameter should be measured in each patient before operation and thus a floating mass transducer with the appropriate caliber should be chosen.
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http://dx.doi.org/10.1097/RCT.0000000000000060DOI Listing
June 2014

Evaluation of the efficacy of curcumin in experimentally induced acute otitis media in rats.

Ann Otol Rhinol Laryngol 2014 May 18;123(5):325-32. Epub 2014 Mar 18.

Yunus Emre State Hospital, Department of Otorhinolaryngology, Eskisehir, Turkey.

Objectives: We investigated the effect of curcumin (CMN) in the treatment of experimentally induced acute otitis media (AOM) in rats.

Method: Thirty-two Sprague-Dawley female rats were used, yielding 64 temporal bones. Group 1 was the control group. For groups 2 to 4, AOM was induced experimentally, and saline, antibiotics (sulbactam-ampicillin), or CMN were administered for 14 days to groups 2, 3, and 4, respectively. During the histological examination, thickening of the tympanic membrane, damage to the epithelium, inflammation, and sclerosis were evaluated.

Results: The AOM+antibiotic and AOM+CMN groups exhibited reduced histological damage compared with the AOM+saline group. No significant differences in thickening of the tympanic membrane or damage to the epithelium or inflammation were observed between the AOM+antibiotic and the AOM+CMN groups. However, the sclerosis values of the AOM+CMN group were significantly lower than those of the AOM+antibiotic group.

Conclusion: CMN treatment resulted in similar effects on the experimentally induced AOM model as did the antibiotic treatment. The efficacy of this treatment may be related to its effects on the production of various inflammatory cytokines. In light of the worldwide increase in antibiotic resistance and the mild side effects of CMN, we suggest that CMN therapy may be a promising option in AOM treatment.
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http://dx.doi.org/10.1177/0003489414525925DOI Listing
May 2014

Computed tomographic findings of X-linked deafness: a spectrum from child to mother, from young to old, from boy to girl, from mixed to sudden hearing loss.

J Comput Assist Tomogr 2014 Jan-Feb;38(1):20-4

From the *Department of Radiology, and †Department of Otorhinolaryngology, Faculty of Medicine, Eskisehir Osmangazi University, Meselik-Eskisehir, Turkey.

Purpose: Congenital mixed hearing loss associated with fixed stapes footplate is a rare disorder transmitted through X-linked inheritance. The purpose of this study was to report the radiologic findings of X-linked deafness with middle ear anomalies in affected children and young patients and in carrier women.

Materials And Methods: The computed tomographic and audiometric findings of 7 subjects (4 affected children and young patients, 1 of whom is a girl; 2 carrier mothers; and a man who presented with sudden hearing loss) from different families were analyzed.

Results: Computed tomography showed bulbous dilatation of the fundi of the internal auditory canals, incomplete bony separation between the basal turn of the cochleas and the lateral ends of the internal auditory canal, deficiency of the modiolus, enlarged first part of the facial nerve, and dilatation of the superior and the inferior vestibular nerve canal and the singular canal. Besides these characteristic findings, dilatation of the vestibular aqueduct was seen except in the man. Middle ear anomalies including oval and/or round window and/or stapes abnormalities were also detected in three affected patients. The carrier mothers had milder forms of some characteristic findings.

Conclusions: Because of the risks of stapes surgery in X-linked deafness, recognition of the characteristic imaging features of these disorders is important. Especially in young patients with mixed hearing loss, temporal bone computed tomography should be performed before stapes surgery to avoid the complication of stapes gusher. Middle ear anomalies might be highly associated with X-linked deafness.
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http://dx.doi.org/10.1097/RCT.0b013e3182a0d05fDOI Listing
March 2014

Investigation of the presence of biofilms in chronic suppurative otitis media, nonsuppurative otitis media, and chronic otitis media with cholesteatoma by scanning electron microscopy.

ScientificWorldJournal 2013 27;2013:638715. Epub 2013 Oct 27.

Department of Otorhinolaryngology, Medical Faculty, Eskisehir Osmangazi University, School of Medicine, 26480 Eskisehir, Turkey.

Objective: Biofilms have been shown to play a major role in the pathogenesis of otolaryngologic infections. However, very limited studies have been undertaken to demonstrate the presence of biofilms in tissues from patients with chronic otitis media (COM) with or without cholesteatoma. Our objective is to study the presence of biofilms in humans with chronic suppurative and nonsuppurative otitis media and cholesteatoma. Study Design. In all, 102 tissue specimens (middle ear, mastoid tissue, and ossicle samples) were collected during surgery from 34 patients.

Methods: The samples were processed for the investigation of biofilms by scanning electron microscopy (SEM).

Results: Our research supports the hypothesis in which biofilms are involved in chronic suppurative otitis media, cholesteatoma, and, to a lesser degree, chronic nonsuppurative otitis media. There were higher rates in hypertrophic and granulated tissue samples than in normal mucosa. In addition, the presence of biofilms was significantly higher in the middle ear mucosa compared with the mastoid and ossicle samples.

Conclusion: In the clinic, the careful use of topical or systemic antimicrobials is essential, and, during surgery, hypertrophic tissue must be carefully removed from normal tissue.
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http://dx.doi.org/10.1155/2013/638715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826458PMC
July 2014

Vocal fold hyperplastic lesions: an evaluation of surgical outcome with videolaryngostroboscopy.

Balkan Med J 2013 Jun 1;30(2):172-7. Epub 2013 Jun 1.

Department of Otorhinolaryngology, Eskişehir Osmangazi University Faculty of Medicine, Eskişehir, Turkey.

Background: Vocal fold hyperplastic lesions are premalignant lesions that can be treated effectively by removal of the lesions surgically.

Aims: The aim of this study was to discuss the success of surgery in patients with vocal fold hyperplastic lesions in terms of preserving vibratory function by comparing the preoperative and postoperative videolaryngostroboscopy findings.

Study Design: The medical charts and videolaryngostroboscopic recordings of patients diagnosed with hyperplastic lesions on the vocal folds were reviewed retrospectively.

Methods: Twenty seven patients with unilateral lesions who underwent type1 subepithelial cordectomy were enrolled in the study. The videolaryngostroboscopic recordings were evaluated by three raters who were not the operating surgeon and who were blinded to the histology of patients. To evaluate the videolaryngostroboscopic findings, a form, which is a modification of criteria described by Hirano and Bless, was used. Preoperative and 6th month postoperative videolaryngostroboscopic recordings were compared with each other and with recordings of the control group, which included 50 healthy volunteers.

Results: All videolaryngostroboscopic findings, except false cord vibration, were significantly improved after surgery.

Conclusion: The principle of vocal fold surgery in patients with benign lesions is to preserve the vibratory tissue. This principle also applies to patients with hyperplastic lesions that are premalignant. The hydrodissection technique may be beneficial for this purpose.
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http://dx.doi.org/10.5152/balkanmedj.2012.113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115964PMC
June 2013

Survival of diced and block cartilage grafts in combination with injectable calcium hydroxylapatite.

Laryngoscope 2013 Nov 13;123(11):E17-22. Epub 2013 May 13.

Department of Otorhinolaryngology, Eskisehir Osmangazi University Medicine Faculty, Eskişehir, Turkey.

Objectives/hypothesis: Dorsal nasal irregularities after trauma, and various procedures such as excessive nasal hump resection, are major problems for patients who have undergone rhinoplasty. Many grafts have been described for the correction of dorsal nasal irregularities. In this study, we used an injectable implant, in combination with diced or block cartilage grafts, to test the efficacy of injectable calcium hydroxylapatite on the survival of diced or block cartilage grafts.

Study Design: Prospective, controlled, parallel group animal study.

Methods: Fourteen New Zealand white rabbits were used. Block cartilage and diced cartilage grafts, alone and in combination with injectable calcium hydroxylapatite, were placed subcutaneously in the rabbits' dorsal thoracolumbar region. On the 90th day following surgery, the graft areas were extracted immediately after the rabbits were sacrificed. Pathological examination was conducted on all specimens.

Results: The pathologic and histochemical findings were compared between groups. There was chronic inflammation observed in all of the groups. However, none of the groups had metaplastic bone formation or calcification. The group that received diced cartilage in combination with the injectable implant received the highest scores for peripheral chondrocyte proliferation, matrix collagen, elastic fiber, and proteoglycan content (P < 0.05). A comparison of the block and diced cartilage grafts revealed that peripheral chondrocyte proliferation was more pronounced in the diced cartilage grafts (P < 0.05).

Conclusion: The use of calcium hydroxylapatite in combination with diced cartilage grafts does not have any long-term negative effects on chondrocyte viability.
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http://dx.doi.org/10.1002/lary.24116DOI Listing
November 2013

Evaluation of nasal airway alterations associated with septorhinoplasty by both objective and subjective methods.

Eur Arch Otorhinolaryngol 2013 Jan 29;270(1):99-106. Epub 2012 Feb 29.

Yunus Emre State Hospital, Eskisehir, Turkey.

The aim of functional septorhinoplasty is to create an esthetically elegant nose and harmony in the face by preserving nasal function as well as maintaining or restoring adequate airway. Since nasal complaints are usually subjective, it may be difficult to evaluate the functions objectively. In the present study, we aimed to investigate the alterations in nasal function associated with septorhinoplasty by using both objective and subjective methods. The study population consisted of 40 patients who underwent septorhinoplasty and 40 healthy controls. Before and after the operation, visual analog scale, acoustic rhinometry, rhinomanometry, and Odiosoft-Rhino test were applied to all patients and controls. There were significant differences in all parameters both before and after the operation. While a significant difference was obtained between the patient and control groups in terms of preoperative values, no significant difference was found between postoperative values of these groups. Both objective and subjective methods are important in evaluations.
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http://dx.doi.org/10.1007/s00405-012-1974-yDOI Listing
January 2013

[Congenital cholesteatoma frequently mistaken for temporal bone dermoid cyst: a case report].

Kulak Burun Bogaz Ihtis Derg 2011 May-Jun;21(3):173-6

Department of Otolaryngology, Medicine Faculty of Eskişehir Osmangazi University, Eskişehir, Turkey.

Dermoid cysts of the middle ear are very rare and can develop behind an intact tympanic membrane, just like congenital cholesteatoma. The visual and clinical symptoms of congenital cholesteatomas and dermoid cysts are difficult to distinguish from each other. Their treatments are similar, however the correct diagnosis can be obtained histopathologically after removing the lesion. In this article a case of a twenty-seven-year-old male patient, whose diagnosis was presumed to be dermoid cyst in the middle ear according to the preoperative radiologic examination but reported to be congenital cholesteatoma as a result of the postoperative histopathologic examination, was reported.
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http://dx.doi.org/10.5606/kbbihtisas.2011.022DOI Listing
December 2011

Sacculocolic reflex in patients with dementia: is it possible to use it for early diagnosis?

Neurol Sci 2012 Feb 11;33(1):17-21. Epub 2011 May 11.

ENT Department, Eskisehir Osmangazi University, Faculty of Medicine, Meselik, 26480 Eskisehir, Turkey.

Alzheimer disease (AD) is a progressive, irreversible entity associated with behavioral changes, memory loss and disturbance of daily life activities. Current diagnostic tools can detect neuronal degeneration in AD only after irreversible damage that already existed. Vestibular evoked myogenic potentials (VEMP) test utilizes the sacculocolic reflex arc and has been used in neuro-otology practice for many years. In this study, we aim to determine if VEMP can be used for diagnostic purposes at the earliest stages of AD. Twenty patients with AD and ten patients with mild cognitive impairment were enrolled in this study. Control group was 30 healthy volunteers with no neurological or otological diseases. Abnormal VEMP responses were found in most of the patients at different stages of AD. VEMP test may be used for early diagnosis of AD. Also, it may provide a novel advancement in understanding of pathophysiology of this disease.
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http://dx.doi.org/10.1007/s10072-011-0595-3DOI Listing
February 2012

Recurrent and private MYO15A mutations are associated with deafness in the Turkish population.

Genet Test Mol Biomarkers 2010 Aug;14(4):543-50

Division of Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey.

The identities and frequencies of MYO15A mutations associated with hearing loss in different populations remained largely unknown. We screened the MYO15A gene for mutations in 104 unrelated multiplex and consanguineous Turkish families with autosomal recessive nonsyndromic sensorineural hearing loss using autozygosity mapping. The screening of MYO15A in 10 families mapped to the DFNB3 locus revealed five previously unreported mutations: p.Y289X (1 family), p.V1400M (1 family), p.S1481P (1 family), p.R1937TfsX10 (3 families), and p.S3335AfsX121 (2 families). Recurrent mutations were associated with conserved haplotypes suggesting the presence of founder effects. Severe to profound sensorineural hearing loss was observed in all subjects with homozygous mutations except for two members of a family who were homozygous for the p.Y289X mutation in the N-terminal extension domain and had considerable residual hearing. We estimate the prevalence of homozygous MYO15A mutations in autosomal recessive nonsyndromic deafness in Turkey as 0.062 (95% confidence interval is 0.020-0.105).
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http://dx.doi.org/10.1089/gtmb.2010.0039DOI Listing
August 2010

Mutations in TMC1 contribute significantly to nonsyndromic autosomal recessive sensorineural hearing loss: a report of five novel mutations.

Int J Pediatr Otorhinolaryngol 2009 May 1;73(5):699-705. Epub 2009 Feb 1.

Division of Clinical Molecular Pathology and Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey.

Genome wide homozygosity mapping using Affymetrix 10K arrays revealed the DFNB7/11 locus including the TMC1 gene in 5 of 35 Turkish families with autosomal recessive nonsyndromic severe to profound congenital or prelingual-onset sensorineural hearing loss (SNHL). Additional 51 families were later screened for co-segregation of the locus with the phenotype using microsatellite markers. GJB2 and mtDNA A1555G mutations were negative in probands from each family. Mutation analysis was performed in families showing co-segregation of autosomal recessive SNHL with haplotypes at the DFNB7/11 locus. A total of six different mutations in seven families were identified, including novel missense alterations, p.G444R (c.1330G>A), p.R445C (c.1333C>T), and p.I677T (c.2030T>C), one novel splice site mutation IVS6+2 T>A (c.64+2T>A), and a novel large deletion of approximately 31kb at the 3' region of the gene including exons 19-24, as well as a previously reported nonsense mutation, p.R34X (c.100C>T). All identified mutations co-segregated with autosomal recessive SNHL in all families and were not found in Turkish hearing controls. These results expand the mutation spectrum of TMC1 with five novel mutations and provide data for the significant contribution of TMC1 mutations in hearing loss.
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http://dx.doi.org/10.1016/j.ijporl.2009.01.005DOI Listing
May 2009

Phenotypic variability of patients homozygous for the GJB2 mutation 35delG cannot be explained by the influence of one major modifier gene.

Eur J Hum Genet 2009 Apr 5;17(4):517-24. Epub 2008 Nov 5.

Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.

Hereditary hearing loss (HL) is a very heterogeneous trait, with 46 gene identifications for non-syndromic HL. Mutations in GJB2 cause up to half of all cases of severe-to-profound congenital autosomal recessive non-syndromic HL, with 35delG being the most frequent mutation in Caucasians. Although a genotype-phenotype correlation has been established for most GJB2 genotypes, the HL of 35delG homozygous patients is mild to profound. We hypothesise that this phenotypic variability is at least partly caused by the influence of modifier genes. By performing a whole-genome association (WGA) study on 35delG homozygotes, we sought to identify modifier genes. The association study was performed by comparing the genotypes of mild/moderate cases and profound cases. The first analysis included a pooling-based WGA study of a first set of 255 samples by using both the Illumina 550K and Affymetrix 500K chips. This analysis resulted in a ranking of all analysed single-nucleotide polymorphisms (SNPs) according to their P-values. The top 250 most significantly associated SNPs were genotyped individually in the same sample set. All 192 SNPs that still had significant P-values were genotyped in a second independent set of 297 samples for replication. The significant P-values were replicated in nine SNPs, with combined P-values between 3 x 10(-3) and 1 x 10(-4). This study suggests that the phenotypic variability in 35delG homozygous patients cannot be explained by the effect of one major modifier gene. Significantly associated SNPs may reflect a small modifying effect on the phenotype. Increasing the power of the study will be of greatest importance to confirm these results.
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http://dx.doi.org/10.1038/ejhg.2008.201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883287PMC
April 2009