Yildirim A. Bayazit

Utilizing Ethnic-Specific Differences in Minor Allele Frequency to Recategorize Reported Pathogenic Deafness Variants

Ethnic-specific differences in minor allele frequency impact variant categorization for genetic screening of nonsyndromic hearing loss (NSHL) and other genetic disorders. We sought to evaluate all previously reported pathogenic NSHL variants in the context of a large number of controls from ethnically distinct populations sequenced with orthogonal massively parallel sequencing methods. We used HGMD, ClinVar, and dbSNP to generate a comprehensive list of reported pathogenic NSHL variants and re-evaluated these variants in the context of 8,595 individuals from 12 populations and 6 ethnically distinct major human evolutionary phylogenetic groups from three sources (Exome Variant Server, 1000 Genomes project, and a control set of individuals created for this study, the OtoDB). Of the 2,197 reported pathogenic deafness variants, 325 (14.8%) were present in at least one of the 8,595 controls, indicating a minor allele frequency (MAF) > 0.00006. MAFs ranged as high as 0.72, a level incompatible with pathogenicity for a fully penetrant disease like NSHL. Based on these data, we established MAF thresholds of 0.005 for autosomal-recessive variants (excluding specific variants in GJB2) and 0.0005 for autosomal-dominant variants. Using these thresholds, we recategorized 93 (4.2%) of reported pathogenic variants as benign. Our data show that evaluation of reported pathogenic deafness variants using variant MAFs from multiple distinct ethnicities and sequenced by orthogonal methods provides a powerful filter for determining pathogenicity. The proposed MAF thresholds will facilitate clinical interpretation of variants identified in genetic testing for NSHL. All data are publicly available to facilitate interpretation of genetic variants causing deafness.

Significance of serotonin transporter gene polymorphism in migraine

OBJECTIVE To elucidate significance of the serotonin transporter gene (STG) polymorphism in migraine, and to address the polymorphic patterns of STG, both in the migraineurs and healthy people in this country. STUDY DESIGN A PCR study of STG in 52 migraineurs and 80 healthy controls. METHODS Using the PCR technique, STG polymorphism was studied in the DNA obtained from leukocytes of the patients and healthy controls. Polymorphism of the two regions (VNTR and 5-HTTLPR) of STG was assessed. RESULTS VNTR STin 2.10 and STin 2.12 alleles were detected in migraineurs and healthy controls. Both homozygous and heterozygous STin 2.10 allele predominated in the migraine group (p=0.01), while STin 2.12 allele was more frequent in the healthy controls (p=0.02). There was no relationship between the migraine type, family history of migraine and STG polymorphism. CONCLUSION STin 2.10 and STin 2.12 alleles of VNTR are frequent in this country. While the presence of STin 2.10 allele increases the risk of migraine, 5-HTTLPR polymorphism is not associated with this risk.

Variations of sphenoid and related structures

Abstract. The aim of this study was to delineate the precise relationship between the sphenoid sinus and internal carotid artery and the optic nerve, as well as to assess incidence of the anatomic variations of these structures. A review of 92 paranasal sinus tomographic scans was made for anatomic variations of the sphenoid sinus and related bony and neurovascular structures. Coronal and axial tomographic sections were obtained with 2.5-mm section thickness. We assessed the protrusion of the internal carotid artery (ICA) and the optic nerve (ON) into the sphenoid sinus, bone dehiscence of these structures, and pneumatization of the anterior clinoid process (ACP) and pterygoid recess (PR), as well as the variations of the sphenoid sinus septum. The protrusion of the ICA into the sphenoid sinus was found in 24 (26.1 %) patients. An ON protrusion was present in 29 (31.5 %) patients. Pneumatization of the PR was encountered in 27 (29.3 %) patients. There was not a statistically significant relationship between the pneumatization of the PR and ICA protrusion into the sphenoid sinus (χ2 = 0.258, p = 0.168). A significant relationship between the ACP pneumatization and protrusion of the ON into the sphenoid sinus was found (χ2 = 0.481, p = 0.007). Preoperative recognition of the anatomic variations by the radiologist is beneficial for identification of the limits of dissection. This is particularly important in the sphenoid sinus area where extensive pneumatization of the skull base bones may distort the anatomic configuration. Therefore, axial and coronal CT sections should always be obtained prior to any surgery in the sphenoid sinus area.

Mycobacterial cervical lymphadenitis.

Cervical lymphadenitis is the most common head and neck manifestation of mycobacterial infections. The incidence of mycobacterial cervical lymphadenitis has increased. It may be the manifestation of a systemic tuberculous disease or a unique clinical entity localized to neck. It remains a diagnostic and therapeutic challenge because it mimics other pathologic processes and yields inconsistent physical and laboratory findings. A high index of suspicion is needed for the diagnosis of mycobacterial cervical lymphadenitis. A unilateral single or multiple painless lump, mostly located in posterior cervical or supraclavicular region can occur. A thorough history and physical examination, tuberculin test, staining for acid-fast bacilli, radiologic examination, fine-needle aspiration and PCR will be instrumental in arriving at an early diagnosis early institution of treatment before a final diagnosis can be made by biopsy and culture. It is important to differentiate tuberculous from nontuberculous mycobacterial cervical lymphadenitis because their treatment protocols are different. Tuberculous adenitis is best treated as a systemic disease with antituberculosis medication. Atypical infections can be addressed as local infections and are amenable to surgical therapy.

Central corneal thickness is lower in osteogenesis imperfecta and negatively correlates with the presence of blue sclera

Background:  Osteogenesis imperfecta (OI) is a rare, autosomal‐inherited, connective tissue disorder characterised by bone fractures, deafness and blue sclera. Additional ocular findings are decreased ocular rigidity, myopia, glaucoma, keratoconus, corneal opacity, small corneal diameter and congenital Bowmans layer agenesis.

Management strategy of mycobacterial cervical lymphadenitis.

The objectives of this study were to investigate the typical clinical presentation, diagnosis and treatment of mycobacterial cervical lymphadenitis (MCL). Medical records of 87 patients who were treated for MCL were retrospectively reviewed. Definitive diagnosis of MCL was made when a neck mass persisted for several weeks or months and one or more of the following was obtained: (1) positive mycobacterial cultures from biopsy material; (2) Positive mycobacterial staining of biopsy material; (3) Granulomatous inflammation and caseating necrosis on histopathological examination of biopsy material. Clinical findings were reviewed prior to treatment. The treatment included standard antituberculous medications followed by surgery in which either total excision or selective nodal dissection of the cervical lump was made. Follow-up results are presented. The chief complaint was a cervical mass that was localized mostly to the posterior cervical or submandibular regions. A fistula formation was encountered in 11.5 per cent. All patients recovered from MCL by combined antituberculous drug and surgical treatments. Clinical presentation of the disease and histopathological assessment are important in the diagnosis of MCL as well as in the differential diagnosis of tuberculous and nontuberculous MCL. Utilizing the combined medical and surgical treatment options, both tuberculous and non-tuberculous cervical adenitis can be treated successfully.

Infrared tympanic thermometer can accurately measure the body temperature in children in an emergency room setting

OBJECTIVE The objective in this study was to compare the accuracy of the tympanic membrane infrared thermometer with the other conventional temperature measurement options. METHODS One hundred and ten randomly selected pediatric patients who admitted to our emergency room were included in the study. Each child underwent simultaneous temperature measurement via rectum, axilla, and external auditory canal. The rectal and axillary measurements were performed using conventional mercury in glass thermometers. The aural measurement was performed using the non-contact infrared thermometer (Braun ThermoScan IRT 1020, Germany). RESULTS On aural measurement, the results of both ears as well as the first, second and third measurements were similar (P<0.01). The mean results of the axillary, rectal and tympanic temperature measurements were 37.46+/-1, 38.18+/-1, and 38.01+/-1.1, respectively. The mean axillary temperature was 0.72 degrees C lower than the mean rectal temperature, and 0.55 degrees C lower than the tympanic temperature. The difference between the mean tympanic and rectal temperatures was 0.17 degrees C. The results of measurements via rectum, axilla and ear were similar (P<0.01). CONCLUSION In conclusion, it is apparent that each of the temperature measurement options has some advantages and disadvantages. An optimal thermometer should have the following features; accurate temperature measurement; ease of application in a short while; safety and absence of potential risks; and tolerability by the patient. Since the aural infrared thermometer meets these criteria, its use in the routine clinical practice appears to be advantageous rather than or complementary to the conventional methods.

Significance of the catechol-O-methyltransferase gene polymorphism in migraine

The objective was to assess the significance of the catechol-o-methyltransferase (COMT) enzyme polymorphism in migraine. For this reason, 62 migraineurs and 64 healthy volunteers were included in the study. The analysis of COMT polymorphism was performed using PCR. The H/H genotype was more frequent in the control group than in the patients group (P=0.032). The homozygous or heterozygous L allele was over represented in the migraineurs compared with the controls (P=0.013). The L/L genotype was over represented in the migraineurs who also had a family history of migraine (P=0.003). There was no relationship between aura and COMT genotypes. In conclusion, the COMT polymorphism may be of potential pharmacological importance regarding the individual differences in the metabolism of catechol drugs in migraineurs. Although altered catecholamine activity due to polymorphism of COMT gene may be one of the mechanisms involved in the pathogenesis of migraine, these mechanisms are not related to presence or absence of aura.

An Overview of Hereditary Hearing Loss

Understanding the genetic basis of hearing loss is important because almost 50% of profound hearing loss are caused by genetic factors and more than 120 independent genes have been identified. In this review, after a brief explanation of some genetic terms (allele, heterozygosis, homozygosis, polymorphism, genotype and phenotype), classification of genetic hearing loss (syndromic versus nonsyndromic, and recessive dominant, X-linked and mitochondrial) was performed. Some of the most common syndromes (Usher, Pendred, Jervell and Lange-Nielsen, Waardenburg, branchio-oto-renal, Stickler, Treacher Collins and Alport syndromes, biotinidase deficiency and Norrie disease) causing genetic hearing loss were also explained briefly. The genes involved in hearing loss and genetic heterogeneity were presented.

Association of the T102C polymorphism of 5-HT2A receptor gene with aura in migraine.

OBJECTIVE To find out the significance of the 5-HT2A receptor gene polymorphism in migraine. STUDY DESIGN A PCR study in which 61 migraineurs and 44 healthy controls were included. METHODS The T102C polymorphism of the 5-HT2A receptor gene was studied. The results of the migraineurs and controls were compared. The relationship between the gene polymorphism and aura was also assessed. RESULTS The representations of the 5-HT2A genotypes were similar in migraineurs and controls (p>0.05) as well as in the male and female migraineurs (p>0.05). The family history of migraine did not associate with 5-HT2A receptor gene polymorphism (p>0.05). There was a significant relationship between the presence of C/C genotype and migraine with aura (p=0.02) while C/T and T/T genotypes were over represented in the patients with migraine without aura (p<0.01). CONCLUSION The T102C polymorphism of the 5-HT2A receptor gene is not directly related to the increased risk of migraine. The associations between the genotypes of this gene and aura may suggest that 5-HT2A receptor gene polymorphism may be involved in determining the subtypes of or accompanying symptoms in the migraine disease.