Unexpectedly high mutation rate of cyp11b1 compared to cyp21a2 in randomly-selected turkish women: a large screening study.

PURPOSE: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders resulting from enzyme deficiencies associated with steroidogenesis. The clinical presentation of non-classic CAH (NCAH) in females is often indistinguishable from other hyperandrogenic disorders like polycystic ovary syndrome (PCOS). The data on the prevalence of NCAH in unselected women in the literature is scanty. The research aimed to evaluate the prevalence of NCAH, carrier frequencies, and the correlation between clinical symptoms and genotype in Turkish women. METHODS: The study group comprised two hundred and seventy randomly-selected unrelated asymptomatic women of reproductive age (18-45). Subjects were recruited from female blood donors. All volunteers underwent clinical examination and hormone measurements. The protein-encoding exons and exon-intron boundaries of the CYP21A2, CYP11B1, HSD3ß2 and CYP21A2 promoter were sequenced by direct DNA sequencing. RESULTS: After genotyping, seven (2.2%) individuals were diagnosed with NCAH. The heterozygous carrier frequencies of CYP21A2, CYP21A2 promoter, CYP11B1, and HSD3ß2 genes with 34, 34, 41, and 1 pathologic mutation were determined at 12.6%, 12.6%, 15.2%, and 0.37% of volunteers, respectively. Gene-conversion (GC) frequencies between CYP21A2/CYP21A1P and CYP11B1/CYP11B2 were determined as 10.4% and 14.8%, respectively. CONCLUSION: Despite GC-derived higher mutation frequency determined in the CYP11B1 gene, the reason for the low frequency of NCAH due to 11OHD compared to 21OHD might be that gene-conversion arises with active CYP11B2 rather than an inactive pseudogene. HSD3ß1 exhibits high homology with HSD3ß2 located on the same chromosome; remarkably, it demonstrates low heterozygosity and no GC, most probably the outcome of a tissue-specific expression pattern.

The role of androgen receptor CAG repeat polymorphism in androgen excess disorder and idiopathic hirsutism.

PURPOSE: The study aimed to investigate whether repeat number in the androgen receptor (AR) gene has any contribution to phenotypes of the disease of androgen excess (polycystic ovary syndrome (PCOS), idiopathic hyperandrogenemia (IHA) and idiopathic hirsutism (IH) in a cohort of Turkish women. METHODS: Three hundred and fifty-four voluntary premenopausal women (172 healthy controls and 182 patients with androgen excess disorders and idiopathic hirsutism) 18-45 years of age seen at an outpatient endocrine clinic at Erciyes University Hospital between January 2013 and December 2014 were included. All volunteers have undergone physical examination and biochemical evaluation. The polymorphic (CAG)n repeat of the human AR was determined by fragment analyses. RESULTS: Detailed clinical analyses of the patients ended up with 137 PCOS, 24 IHA, and 21 IH. Pairwise comparisons revealed the CAG repeat number differences between the PCOS and controls (p = 0.005) and IH and controls (p = 0.020). Women with CAG repeat length ≤ 17 had a significantly increased twofold risk for PCOS than those women with > 17 CAG repeats OR: 2.0 (95% CI 1.2-3.3, p = 0.005). Women with CAG repeat length ≤ 17 had a significantly increased threefold risk for IH than those women with > 17 CAG repeats OR: 2.9 (95% CI 1.2-7.3, p = 0.020). When correlation analysis was performed, a weak negative correlation was detected between the short allele and FGS score (r = - 0.131, p = 0.013) and a positive relationship between total testosterone and longer allele in the IHA group (r = 0.425, p = 0.039). Median repeat length of the shorter allele between oligomenorrhea and woman with normal menstrual cycle was found to be statistically significant (p = 0.017). CONCLUSION: This study indicated that the risk of PCOS and IH is associated with the inheritance of ARs with shorter CAG repeats.

Comprehensive genotyping of Turkish women with hirsutism.

INTRODUCTION: Hirsutism is a medical sign rather than a disease affects 5-8% of women of reproductive age. Hirsutism is associated with hyperandrogenemia in most patients excluding those with idiopathic hirsutism (IH). The most common cause of hirsutism is polycystic ovary syndrome (PCOS) followed by IH and idiopathic hyperandrogenemia (IHA); however, the clinical presentation of non-classical congenital adrenal hyperplasia (NCAH) in females is often indistinguishable from other hyperandrogenic disorders with common clinical signs such as hirsutism. OBJECTIVE: The primary aim of the study is to examine the physical properties of the three genes and to make a detailed comparison of the mutations with the clinical data to contribute the etiology of hirsutism. SUBJECTS AND METHODS: 122 women admitted to the Endocrinology Clinic at Erciyes University Hospital with hirsutism were enrolled in the study between 2013-2014. All the participants were clinically evaluated. Protein-encoding exons, exon-intron boundaries of CYP21A2 (including proximal promoter), CYP11B1 and HSD3B2 genes were analyzed via state-of-the-art genetic studies. RESULTS: DNA sequencing analyses revealed two homozygous and three compound heterozygous 21-hydroxylase deficient (21OHD) NCAH patients. Additionally, three novel CYP21A2 mutations (A89V, M187I and G491S) and two novel CYP11B1 mutations (V188I and G87A) were determined. The frequencies of heterozygous mutations in CYP21A2 (including promoter), CYP11B1 and HSD3B2 genes were determined as 26.5% (15% coding region, 11.5% promoter), 11.5% and 0%, respectively. CONCLUSION: 21OHD-NCAH prevalence was determined to be ~4%. Unexpectedly, high heterozygous mutation rates were observed in CYP11B1 gene and CYP21A2 promoter region. CYP11B1 and HSD3B2 deficiencies were not prevalent in Turkish women with hirsutism despite the existence of higher heterozygous mutation rate in CYP11B1.

Expression of Glutamate Transporters in Alcohol Withdrawal.

INTRODUCTION: The study aimed to investigate the expression of glutamate transporters during withdrawal in the alcohol-dependent patients. METHOD: The study consisted of 20 male inpatient alcoholics during the withdrawal period and 20 healthy controls. Expressions of glutamate transporters, namely the excitatory amino acid transporter 2 (EAAT2) and EAAT3, in white blood cells were measured with the real-time polymerase chain reaction (RT-PCR) method in early (first day) and late (28(th) day) withdrawal in alcoholic patients and once in the controls. RESULTS: EAAT2 and EAAT3 expressions in the patients during both early and late withdrawal were higher than those of the controls. There was no difference in the EAAT2 and EAAT3 levels of the patients between early and late abstinence. DISCUSSION: The study revealed an upregulation of glutamate transporters EAAT2 and EAAT3 during early and late withdrawal in patients with alcohol withdrawal.

Diagnosis of allergic rhinitis: inter-rater reliability and predictive value of nasal endoscopic examination: a prospective observational study.

OBJECTIVE: To determine the inter-rater reliability of nasal endoscopic findings and the feasibility of diagnosis of allergic rhinitis based solely on symptoms and nasal endoscopy. DESIGN: Prospective observational study. SETTING: University Teaching hospital. PARTICIPANTS: One hundred and eight patients were referred from the allergy clinic included in the study. MAIN OUTCOME MEASURES: Predictive value of symptoms and nasal endoscopic examination to diagnose allergic rhinitis and inter-rater reliability of the examination were evaluated. RESULTS: Logistic regression analysis of patient symptoms and nasal examination findings revealed no significant predictive power for any of the symptoms or examination findings. The Fleiss κ coefficient of the three raters was calculated. Inter-rater variability among the three physicians demonstrated that mucosal oedema (κ = 0,48, P < 0.001), polypoid degeneration of the inferior turbinate tail (κ = 0.48, P = 0.01), nasal polyps (κ = 0.96, P < 0.001) and nasal septal deviation (κ = 0.65, P = 0.01) showed significant inter-rater agreement. A low κ coefficient (0.29) was found, and the inter-rater variability among physicians in interpreting the characteristics of nasal secretions was significant (P = 0.04). The inter-rater variability among the three physicians suggested that turbinate hypertrophy (κ = 0.31) and turbinate colour (κ = 0.38) showed no significant inter-rater agreement. CONCLUSIONS: Patient symptoms and nasal endoscopy findings do not provide reliable diagnosis of allergic rhinitis. Turbinate colour and hypertrophy are believed to be related to allergic rhinitis; however, these were subject to marked inter-rater variability in this study.

Can the classical euchromatic variants of 9q12/qh+ cause recurrent abortions?

Various heteromorphisms of the 9q heterochromatic area have been reported, and the 9q12/qh variant has been postulated to be more prevalent than initially perceived. Of note is that all probands are clinically normal. This paper documents two cases with a G-band within the 9q12h region and recurrent miscarriages. Patient 1 is a 22-year-old woman with a history of 2 miscarriages. Patient 2 is a 19-year-old woman with a history of 3 miscarriages. Chromosome analysis of the patients showed 46,XX,9q12h+. Thus, the existence of a G+ band in 9qh may not be a normal variant in humans. We suggest IVF and preimplantation genetic diagnosis in such patients.

Effect of surgical intervention on middle-ear cholesteatoma with associated facial paralysis.

OBJECTIVES: To investigate the presenting symptoms, intra-operative findings and long-term facial nerve function in patients treated for cholesteatoma with associated facial paralysis. METHODS: Fifteen patients with facial paralysis due to middle-ear cholesteatoma who underwent tympanomastoidectomy surgery from February 2000 to February 2015 were retrospectively reviewed. After removal of the cholesteatoma, a limited area of the fallopian canal, in which facial nerve oedema or redness was evident, was opened. Incision of the epineural sheath for nerve decompression was not performed. RESULTS: Pre-operative House-Brackmann grade was grade II in two patients, grade III in four, grade IV in seven, grade V in one and grade VI in one. Facial nerve perineurium damage was observed in two patients with poor prognoses. All patients treated within the first 15 days after paralysis onset showed normal facial function at long-term follow up. Post-operative House-Brackmann grade was grade I in 11 patients, grade II in 1, grade III in 2 and grade VI in 1. CONCLUSION: Early surgical treatment is more likely to give good results, and poor outcomes are observed in patients with facial nerve perineurium damage.

Genotoxic potential of Turkish propolis in peripheral blood lymphocytes.

Propolis is a natural product that is collected by the honeybee (Apis mellifera L.) from plants. The in vitro genotoxic potential of propolis in human lymphocytes was investigated. Blood samples were obtained from ten healthy (five female and five male), non-smoking and alcohol volunteers, which were incubated and exposed to increasing concentrations of propolis (5, 25, 50 and 250 mg/ml). The mean sister chromatid exchange (SCE) rates were 10.398 +/- 1.47-21.522 +/- 2.08. The differences between the control and exposed cells were statistically significant (p < 0.05). Increasing SCE rates showed that propolis could have genotoxic effects in high concentrations. SCE rates of women donors exceeded those of men donors. Women donors had the highest SCE rates (25.674 +/- 8.71, 22.456 +/- 7.97 and 15.756 +/- 5.09 for mean of SCE).

Early stage squamous cell carcinoma of the lower lip: predictive factors for recurrence.

OBJECTIVE: This study aimed to evaluate the effect of tumour thickness on other clinicopathological parameters in early stage lower lip squamous cell carcinoma. METHODS: Forty-six consecutive patients with lower lip squamous cell carcinoma were included in the study. Demographic, clinical and pathological data were retrospectively collected. RESULTS: The mean follow-up period for all patients was 32.0 ± 18.9 months. Forty-four tumours were staged as T1 and two were T2. Twelve patients underwent neck dissection. Two patients presented with neck metastasis in the follow-up period. Four patients (8.7 per cent) had local recurrence. Correlation analysis revealed a significant relationship between microscopic tumour thickness and local tumour recurrence (r = 0.328, p = 0.045). CONCLUSION: Surgical margin control is important to prevent local recurrence, especially in thicker tumours. In addition, neck metastasis is rare in early stage lower lip squamous cell carcinoma. A 'wait and see' policy might be preferred in early stage T1 lower lip squamous cell carcinoma cases.

5,10-Methylenetetrahydrofolate reductase C677T gene polymorphism in Behcet's patients with or without ocular involvement.

BACKGROUND: Increased serum levels of homocysteine (Hcy) have been reported in patients with Behçet's disease (BD) with an established risk factor for vascular involvement. Recently, the authors demonstrated that elevated Hcy levels are associated with ocular involvement in such patients. On the other hand, elevated levels of Hcy can result from genetic errors. Indeed, a mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR C677T) gene influences Hcy metabolism and, therefore, MTHFR C677T polymorphism provokes hyperhomocysteinaemia. AIM: To investigate the possible genetic factor for the elevation of plasma Hcy level in patients with BD by examining gene interaction with the MTHFR C677T polymorphism, a crucial factor of the Hcy metabolism. In addition, the authors aimed to evaluate if there is an association between the C677T polymorphism and the presence of ocular involvement in such patients. METHOD: A total of 59 patients with BD (25 men, 34 women) with a mean age of 34.9 years and 42 age and sex matched healthy control subjects (19 men, 23 women; mean age 32.2) were included in this investigation. MTHFR gene polymorphism was investigated by the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) of a genomic DNA fragment at nucleotide 677 in all subjects in both groups. The genetic equilibrium is assumed for the gene frequencies of the MTHFR polymorphism in both samples. RESULTS: The genotype of the MTHFR gene differed between the Behçet's patients and control subjects (TT: 11.9 v 2.4%; CT: 55.9 v 61.9%; CC: 32.2 v 35.7 %). TT homozygous genotype was more frequently in BD patients than the controls, though the difference was not significant (p = 0.063). In BD patients with ocular involvement, however, the frequencies of MTHFR TT homogenetic type (27.8%) were significantly and statistically higher than those in BD patients without ocular involvement (4.9%, p = 0.022, odds ratio = 7.5), or the controls (2.4%, p = 0.003, odds ratio = 20.0). TT homozygous genotype was associated with an increased risk for ocular involvement. CONCLUSION: Elevated serum levels of Hcy seem to be a result of C677T polymorphism of the MTHFR gene, with increased TT individuals over CC and CT genotype BD patients. Although no association was shown between the MTHFR reductase C677T polymorphism and the increased risk of oral aphtahe or genital ulcers, a mutation in this gene was associated with an increased risk of ocular involvement, suggesting genetic instability with a potential initiation of Hcy lowering therapy in this patient group.

A novel acropectoral syndrome maps to chromosome 7q36.

F syndrome (acropectorovertebral syndrome) is a dominantly inherited skeletal dysplasia affecting the hands, feet, sternum, and lumbosacral spine, which has previously been described in only two families. Here we report a six generation Turkish family with a related but distinct dominantly inherited acropectoral syndrome. All 22 affected subjects have soft tissue syndactyly of all fingers and all toes and 14 also have preaxial polydactyly of the hands and/or feet. In addition, 14 have a prominent upper sternum and/or a blind ending, inverted U shaped sinus in the anterior chest wall. Linkage studies and haplotype analysis carried out in 16 affected and nine unaffected members of this family showed that the underlying locus maps to a 6.4 cM interval on chromosome 7q36, between EN2 and D7S2423, a region to which a locus for preaxial polydactyly and triphalangeal thumb-polysyndactyly has previously been mapped. Our findings expand the range of phenotypes associated with this locus to include total soft tissue syndactyly and sternal deformity, and suggest that F syndrome may be another manifestation of the same genetic entity. In mice, ectopic expression of the gene Sonic hedgehog (Shh) in limb buds and lateral plate mesoderm during development causes preaxial polydactyly and sternal defects respectively, suggesting that misregulation of SHH may underlie the unusual combination of abnormalities in this family. A recently proposed candidate gene for 7q36 linked preaxial polydactyly is LMBR1, encoding a novel transmembrane receptor which may be an upstream regulator of SHH.

Outcomes with gold wire and hydroxyapatite partial ossicular replacement prostheses in type 2 tympanoplasty: a preliminary study.

OBJECTIVES: To compare the hearing results and graft take rates of the recently developed gold wire prosthesis with those of the hydroxyapatite partial ossicular replacement prosthesis in patients with chronic otitis media. METHOD: This retrospective study examined patients who underwent type 2 tympanoplasty with a minimum follow up of one year. The study population consisted of 32 patients in the partial ossicular replacement prosthesis group and 26 patients in the gold wire group. The main outcome measures were the graft success rate and level of hearing improvement. Complications and extrusion rates were also noted. RESULTS: The graft take rate was 90.6 per cent for the partial ossicular replacement prosthesis group and 92.3 per cent for the gold wire group (p = 0.848). Pre-operatively, there were no significant differences in the air or bone-conduction thresholds between groups. Post-operatively, the mean hearing gain was 18.5 ± 14.0 dB in the partial ossicular replacement prosthesis group and 16.5 ± 10.6 dB in the gold wire group (p = 0.555). The mean air-conduction thresholds were 26.6 ± 12.4 and 32.6 ± 10.5 dB, respectively (p = 0.027), and the mean bone-conduction thresholds were 9.7 ± 7.0 and 10.4 ± 6.4 dB, respectively (p = 0.687). CONCLUSION: The success and complication rates provided by the gold wire prosthesis seem comparable to those of the hydroxyapatite partial ossicular replacement prosthesis.

Female-to-male transsexual with 47,XXX karyotype.

BACKGROUND: There are few reports describing chromosomal abnormalities in transsexuals. In rare cases, transsexualism and sexual chromosomal multiplicity coexist. Six cases of male-to-female transsexuals with 47,XYY chromosomal pattern have been previously reported. We have not encountered any female transsexual cases with 47,XXX karyotype in the literature. METHODS: A 21-year-old female patient came to our outpatient department with depressive symptoms and suicidal thoughts. On psychiatric interview, she reported that she had feelings of discomfort with her gender identity and had desired to be male since her childhood. Then, we performed cytogenetic investigation using blood culture and G chromosome banding. RESULTS: Histology and DNA histograms of the patient revealed a chromosomal pattern of 47,XXX. CONCLUSIONS: We conclude that sexual chromosomal abnormalities in some transsexuals may cause a vulnerability to development of a gender identity disorder.

Sister chromatid exchange frequency in inhabitants exposed to asbestos in Turkey.

Pleural mesothelioma, lung cancer, pleural calcification and fibrosis have been observed among inhabitants of the villages in Ivriz-Zanapa valley in Turkey. Earlier reports have stated that these endemic pathological conditions are caused by the inhalation of actinolite asbestos, a mineral commonly used indiscriminately to paint the walls and floors of houses. In the present study, 40 inhabitants in Yassikaya village in Ivriz-Zanapa valley and 20 controls were further investigated. The peripheral blood lymphocytes were cultured and harvested at 72 h for sister chromatid exchange (SCE) frequency. Inhabitants had a raised mean SCE rate compared with a control population.

Sister-chromatid exchange inducing effect of smokeless tobacco using on T-lymphocyte chromosomes.

A kind of a smokeless tobacco (Maras powder) is widely used instead of cigarettes in the South Eastern region of Turkey. In this study we investigated the sister-chromatid exchange (SCE) inducing effect of this powder on the chromosomes of its users compared with smokers and nonsmokers using standard cell culture methods and SCE staining techniques. Average SCE per metaphase and total SCEs increased significantly among both smokeless tobacco users and smokers compared to nonsmokers (p < 0.01). However, the effect is significantly lower in smokeless tobacco users than in smokers (p < 0.05).

Associated anomalies in asymmetric crying facies and 22q11 deletion.

Congenital asymmetric crying facies, a minor congenital anomaly due to unilateral absence or hypoplasia of the depressor anguli oris muscle, is associated at times with major congenital anomalies. A large number of asymmetric crying facies cases with chromosome 22q11 microdeletions have presently been reported. Fluorescence in situ hybridization (FISH) analysis for 22q11 deletion was performed on 8 infants with asymmetric crying facies. Five of our patients had at least one associated systemic anomaly. Two of 5 patients had conotruncal heart disease (Cayler cardiofacial syndrome). In three of the affected infants, we failed to reveal additional congenital malformation. The 22q11 deletion was present in only one patient. This baby had congenital hypoparathyroidism, severe neonatal hypocalcaemia and tetralogy of Fallot. We suggest, a 22q11 deletion should be excluded not in all cases but in cases with Cayler cardiofacial syndrome and in ACF associated with additional congenital anomalies.

Increased sister chromatid exchanges in workers exposed to occupational lead and zinc.

Sister chromatid exchange (SCE) in blood lymphocytes was determined in 32 male workers occupationally exposed to lead (Pb) and zinc (Zn) and in 20 controls matched for age and smoking habits. Exposed workers have higher SCE mean values than control workers (p < 0.01). In exposed persons, blood Pb concentrations were also significantly higher than controls (p < 0.0001), but the difference between Zn levels in the blood of these groups was not found to be significant (p > 0.05). Our results indicate that Pb may be genotoxic and harmful to human health.

Do non-steroidal anti-inflammatory drugs induce sister chromatid exchanges in T lymphocytes?

The genetic toxicity of non-steroidal anti-inflammatory drugs was investigated using the sister chromatid exchange technique in cultured human lymphocytes. A total of 48 patients were treated with non-steroidal anti-inflammatory drugs (ibuprofen, ketoprofen, naproxen, indomethacin, diclofenac or acetylsalicylic acid) for 2 weeks. The average numbers of sister chromatid exchanges in cultured lymphocytes from the patients, before and after treatment with these drugs, did not differ significantly (P > 0.05). These results indicate that treatment with non-steroidal anti-inflammatory drugs for 2 weeks does not induce sister chromatid exchanges in T lymphocytes.

A case with Waardenburg syndrome presenting with two separate translocations--one reciprocal and one complex.

A 2-month-old Turkish male with Waardenburg syndrome who has two de novo translocations is described. The translocations are a reciprocal translocation between chromosomes 1 and 8, and a more complex translocation involving chromosomes 4 and 7.