Mahmut Selman Yildirim

Chromosome 8 Aneuploidy in Acquired Cholesteatoma

Objective To investigate the incidence of chromosome 8 aneuploidy in acquired cholesteatoma. Material and Methods Cholesteatoma tissue and postauricular skin as a control were surgically obtained from 12 patients with acquired cholesteatoma. Fluorescence in situ hybridization (FISH) analysis using a chromosome 8-specific α-satellite DNA probe was performed on the interphase nuclei. Two hundred cells were analyzed for each of the samples. Results Chromosome 8 aneuploidy was found in 9/12 patients whereas a normal cell structure with 2 signals was observed in the remaining 3 patients. In samples with chromosome 8 aneuploidy, the mean proportion of aneuploidy was 25.6%, including monosomy (3.2%), trisomy (16.1%), tetrasomy (4.9%) and more than tetrasomy (1.4%). The number of aneuploid cells in recurrent cases was more than that in non-recurrent cases. Conclusion A numerical aberration of chromosome 8 was found in patients with acquired cholesteatoma. Our results support the hypothesis that chromosome 8 may be a prognostic factor for cholesteatoma and an indicator in the follow-up of patients with cholesteatoma.

Evaluation of c-MYC status in primary acquired cholesteatoma by using fluorescence in situ hybridization technique.

Objective: The object of study was to investigate the status of c-MYC oncogene in primary acquired cholesteatoma. Study design: Descriptive study. Methods Cholesteatoma samples were obtained from 15 patients with primary acquired cholesteatoma during surgical operation. Fluorescence in situ hybridization with a mixed DNA probe, which is specific for c-MYC located on 8q24 and chromosome 8 specific-alpha-satellite DNA probe (dual color), was used on the interphase nuclei. Results: Copy number of c-MYC oncogene and aneuploidy of chromosome 8 were 21.2% ± 14.4% and 21.7% ± 14.8%, respectively. There was no significant difference between copy number of c-MYC and frequency of chromosome 8 aneuploidy (p > 0.05). Ten of 15 cases showed different percentage of c-MYC and chromosome 8 aneuploidy, whereas 5 (33.3%) of 15 cases showed a normal distribution of c-MYC and chromosome 8 signals. Conclusion: The copy number of c-MYC in 10 of 15 cases was found to be high as observed for chromosome 8 aneuploidy in primary acquired cholesteatoma. These findings suggest that the ability of hyperproliferation of primary acquired cholesteatoma might have been related to c-MYC copy number by deregulating c-MYC expression.

GAPO syndrome: Four new patients with congenital glaucoma and myelinated retinal nerve fiber layer†‡

This article reports on the ophthalmological features of four Turkish children with GAPO syndrome, a very rare autosomal recessive condition characterized by growth retardation (G), alopecia (A), pseudoanodontia (P) (failure of tooth eruption), and optic atrophy (O). The children were from two unrelated families born to consanguineous parents. They had the characteristic facial appearance of alopecia, rarefaction of eyebrows and eyelashes, frontal bossing, high forehead, midfacial hypoplasia, hypertelorism, and thickened eyelids and lips. Two children had severe end‐stage glaucoma in both eyes and unilateral corneal opacity, whereas other two children had myelinated retinal nerve fiber layer; one with bilateral optic atrophy and the other one with persistent pupillary membrane in the left eye.

Hypogammaglobulinemia and Silver–Russell phenotype associated with partial trisomy 7q and partial monosomy 21q†

Hypogammaglobulinemia and Silver–Russell Phenotype Associated With Partial Trisomy 7q and Partial Monosomy 21q Hasibe Artac,* Ismail Reisli, Mahmut Selman Yildirim,† Gulseren Bagci, Guven Luleci, Orhan Hosgor, and Sevim Karaaslan Department of Pediatrics, Division of Immunology and Allergy, Selcuk University Meram Medical Faculty, Konya, Turkey Department of Genetics, Selcuk University Meram Medical Faculty, Konya, Turkey Department of Genetics, Akdeniz University Medical Faculty, Antalya, Turkey Department of Obstetrics and Gynecology, Antalya Government Hospital, Antalya, Turkey Department of Pediatrics, Division of Cardiology, Selcuk University Meram Medical Faculty, Konya, Turkey

Would mean platelet volume/platelet count ratio be used as a novel formula to predict 22q11.2 deletion syndrome?

BACKGROUND The diagnosis of 22q11.2 deletion syndrome depends on a time-consuming and expensive method, fluorescence in situ hybridisation (FISH). OBJECTIVES We aimed to determine new parameters which can aid for in the diagnosis of 22q11.2 deletion syndrome. METHODS Twenty two patients with 22q11.2 or 10p13 deletion were evaluated retrospectively. RESULTS Facial-dysmorphism and mental-motor retardation were detected in 100% of patients. Mean platelet (PLT) counts were lower (224,980 versus 354,000, p = 0.001), mean PLT volume (MPV) (9.95 versus 7.07, p = 0.002), and MPV/PLTx105 ratios (5.36 versus 2.08, p < 0.001) were higher in patients with 22q11.2 deletion compared with the control group. Area under the receiver-operator characteristic (ROC) curve was 0.864, sensitivity was 84.6%, specificity was 90.9%, positive predictive value (PPV) was 91.7%, and negative predictive value (NPV) was 83.3% when MPV was 8.6. Area under ROC curve was 0.864, sensitivity was 76.9%, specificity was 90.1%, PPV was 90.1%, and NPV was 76.3% when PLT was 265,500. Area under ROC curve was 0.906, sensitivity was 84.6%, specificity was 100%, PPV was 100%, and NPV was 84.6% when MPV/PLTx105 was 3.3. Expression of PLT surface markers which were not in the GPIb-V-IX receptor complex (CD61, CD41a) increased as the surface area increased, but markers which were in a complex (CD42a, CD42b) did not change. CONCLUSIONS High MPV/PLT value can be a good predictor for the diagnosis of 22q11.2 deletion syndrome. We suggest that in patients with facial dysmorphism and retardation in neurodevelopmental milestones and if MPV≥8.6fl, MPV/PLTx105 ratio≥3.3 and PLT count ≤265,500/mm3, the patients should be tested by FISH analysis to confirm the 22q11.2 deletion. If there are no macrothrombocytes, the 10p13 deletion should be tested in suspected cases.

NAT2 Gene Polymorphisms in Turkish Patients with Psoriasis Vulgaris.

Psoriasis is a common, chronic, and autoimmune skin disease. Factors that play a role in etiopathogenesis of psoriasis include internal factors such as genetic susceptibility and immunological factors and external factors such as stress, infection, trauma, drug, and environmental compounds. N-acetyltransferase 2 (NAT2) is a xenobiotic enzyme that is involved in the metabolism of drugs, environmental toxins, and carcinogens. In this study, we aimed to demonstrate whether the variations in the NAT2 gene lead to a predisposition to psoriasis by affecting the enzymes ability to metabolize drugs and environmental components or not. Three polymorphisms (rs1799929, rs1799930, and rs1799931) in NAT2 gene were genotyped and compared by real-time PCR method in 260 psoriasis vulgaris patients and 200 healthy controls. There was no difference in the genotype distributions and allele frequencies of polymorphisms between psoriasis vulgaris patients and controls. When the effects of polymorphisms on the clinical features of the disease, such as onset age and severity, are assessed, it has been found that rs1799930 and rs1799929 are, respectively, associated with early onset age and severity of the disease. In conclusion, rs1799929, rs1799930, and rs1799931 polymorphisms of the NAT-2 gene do not appear to be a risk factor for the development of psoriasis. Conversely, they may have an effect on either more severe or early onset cases of the disease.

Ocular Findings in Children With 22q11.2 Deletion Syndrome

PURPOSE To identify the ocular features of children diagnosed as having 22q11.2 deletion syndrome in a Turkish population, which is the most common microdeletion syndrome with a wide range of facial and ocular abnormalities. METHODS Sixteen children aged between 4 months and 18 years with a microdeletion in chromosome 22q11.2 underwent a detailed ophthalmological examination including uncorrected and best corrected visual acuity testing, stereoscopic vision examination, biomicroscopic and indirect fundus examination, and ocular motility testing. RESULTS All patients had at least one ocular abnormality. The major abnormalities were eyelid abnormalities (eye hooding, narrow palpebral fissure, telecanthus, hypertelorism, sparse and thin eyebrows and eyelashes, blepharitis, and distichiasis), posterior embryotoxon, and tortuous retinal vessels in at least half of the patients. Other ophthalmological disorders were refractive errors, iris remnants, and strabismus. CONCLUSIONS The chromosome 22q11.2 deletion syndrome is associated with a wide range of ocular disorders, which necessitates a comprehensive eye examination for appropriate treatment and follow-up. Ocular findings sometimes can provide a clue to the diagnosis of 22q11.2 deletion. [J Pediatr Ophthalmol Strabismus. 2016;53(4):218-222].

Frequency of BsmI polymorphism of vitamin D receptor gene and its association with 25-hydroxyvitamin D levels

INTRODUCTION Vitamin D deficiency has become a major public health problem. It’s known that the effects of vitamin D are made by its receptors. Vitamin D receptor (VDR) is a member of nuclear receptors type 1 such as androgen, estrogen, progesterone and glucocorticoid receptor. In several studies carried out up to 30 different cells and tissues of the vitamin D receptor (VDR) have shown the presence. In many studies ongoing malignancies and their relationship with Vitamin D and VDR are being investigated. VDR gene polymorphisms in susceptibility to different diseases demonstrated in many studies. The polymorphisms of VDR are ApaI, TaqI, FokI and BsmI. BsmI is the most extensively studied polymorphism. In a study conducted for osteoporosis BB genotype was reported to be low risk indicator [1]. In our study, the aim is to show the frequency of VDR BsmI gene polymorphisms and to show the relationship between polymorphisms and vitamin D levels. METHOD All population were divided into two groups which are 100 osteoporotic and 100 non-osteoporotic. The demographic characteristics were recorded. In blood samples vitamin D, calcium, phosphorus, alkaline phosphatase; in urine samples urinary calcium, urinary creatinine were studied. In addition, approximately 2 cc of peripheral blood sample was taken for DNA isolation and VDR BsmI polymorphisms were studied by real-time PCR method and comparisons were made between the groups. RESULTS In all of population BB genotype 17 %, Bb genotype 50.5 % and bb genotype 32.5 % were found. In osteoporotic grup BB genotype 16 %, Bb genotype 48 % and bb genotype 36 % were found. In non-osteoporotic grup BB genotype 18 %, Bb genotype 53 % and bb genotype 29 % were found. There was no statistically significant difference between groups (p=0.571). The level of vitamin D was 18.10 ng/mL in BB genotype, 17.08 ng/mL in Bb genotype and 16.34 ng/mL in bb genotype. There was no statistically significant difference between genotypes (p=0.717). Fig 1: Vitamin D levels in genotypes Fig 2: Allels in Groups