-
Clinical dysmorphology 05/2013; · 0.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Silver-Russell syndrome (SRS) is a clinically and genetically heterogeneous syndrome which is characterized by severe intrauterine and postnatal growth retardation, and typical characteristic facial dysmorphisms. It has been associated with maternal uniparental disomy (UPD) for chromosome 7 and hypomethylation of imprinting control region 1 (IGF2/H19) in 11p15. UPD refers to the situation in which both copies of a chromosome pair have originated from one parent. UPD can be presented both as partial heterodisomy and isodisomy. The aim of this study was to determine the maternal UPD7 (matUPD7) in 13 Turkish SRS patients.
Genotyping for matUPD7 was performed with microsatellite markers by polymerase chain reaction.
The maternal UPD7 including the entire chromosome was identified in 1/13 (7.6%) of individuals within SRS patients. There were no significant differences between clinical features of matUPD7 case and other SRS cases except congenital heart defects.
It is often difficult to establish diagnosis of a child with intrauterine growth retardation (IUGR), growth failure and dysmorphic features. Thus, screening for matUPD7 in IUGR children with growth failure and mild SRS features might be a valuable diagnostic tool.
Iranian Journal of Pediatrics 12/2012; 22(4):445-51. · 0.29 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: The imbalance between pro-inflammatory and anti-inflammatory cytokines may possibly play a role in the development of bronchopulmonary dysplasia (BPD) in preterm infants. Mannose binding lectin (MBL) codon 54 and interleukin 1 receptor antagonist gene (IL1-RN) polymorphisms cause genetic predisposition to increased risk of infection and inflammation, therefore may increase the risk of BPD. The aim of the study was to investigate the relationship between MBL, IL1-RN gene polymorphisms and BPD development in preterm infants. METHODS: MBL codon 54 and IL1-RN polymorphisms were studied in 71 infants who were born at less than 32 weeks of gestation, with the diagnosis of BPD (Group 1) and control group of preterm infants without BPD (Group 2). RESULTS: IL1-RN and MBL2 variant genes were closely associated with the increased risk of BPD (both of them p<0.001) together with significantly lower birth weights (p<0.001 and p=0.001, respectively), lower 5-minute Apgar scores (p=0.009 for both genes) and increased neonatal infection rates (p<0.001 and p<0.009, respectively).IL1 RN 1/1 genotype was protective (OR, 0.075; 95% CI, 0.019-0.76) while IL1-RN 2/2 genotype increased the risk for BPD (OR, 11.7; 95% CI, 1.3-103.6). MBL-AA genotype was protective against BPD (OR, 0.066; 95% CI, 0.02-0.2) whereas MBL-BB genotype increased the susceptibility for the development of BPD (OR, 23.8; 95% CI, 2.8-200.6). CONCLUSIONS: MBL and IL 1 RN polymorphisms were found closely related with low birth weights, increased the risk of neonatal sepsis and BPD development in preterm infants.
Pediatrics International 08/2012; · 0.63 Impact Factor
-
Clinical and Applied Thrombosis/Hemostasis 06/2012; 18(3):327-30. · 1.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hemoglobinopathies, especially β-thalassemia (β-thal), represent an important health burden in Mediterranean countries like Turkey. Some couples prefer the option of preimplantation genetic diagnosis (PGD). However, clinical application of PGD, especially for the monogenic disorders is technically demanding. To ensure reliable results, protocols need to be robust and well standardized. Ideally PGD-PCR (polymerase chain reaction) protocols should be based on multiplex and fluorescent PCR for analysis of the disease-causing mutation(s) along with linked markers across the disease-associated locus. In this study, we aimed to constitute a protocol in single cells involving first round multiplex PCR with primers to amplify the region of the β-globin gene containing the most common mutations. Two microsatellites linked to the β-globin gene cluster (D11S4891, D11S2362) and two unlinked (D13S314, GABRB3) microsatellite markers, were used to rule out allele dropout (ADO) and contamination; followed by nested real-time PCR for genotyping the β-globin mutations. We also investigated the allele frequencies and heterozygote rates of these microsatellites in the Turkish population that have not been reported to date. This protocol was tested in 100 single lymphocytes from heterozygotes with known β-globin mutations. Amplification failure was detected in one lymphocyte (1%) and ADO was observed in two lymphocytes (2%). No contamination was detected. All results were concordant with the genotypes of the patients. Overall, this protocol was demonstrated to be sensitive, accurate, reliable and rapid for the detection of β-globin mutations in single cells and shows potential for the clinical application of PGD for hemoglobinopathies in the Turkish population.
Hemoglobin 04/2012; 36(3):230-43. · 1.30 Impact Factor
-
Journal of Neuro-Oncology 03/2012; 107(3):665. · 3.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Mannose-binding lectin is an important component of innate immunity; it initiates the lectin pathway of complement activation critical for innate immunity. Failure of local innate defenses may result in defective responses that lead to the persistent carriage of microorganisms or ongoing inflammation. This study investigated the role of mannose-binding lectin levels and the frequency of the 6 functional mannose-binding lectin polymorphisms in Turkish individuals with nasal polyposis.
A case-control study.
University hospital.
Fifty-one patients with nasal polyposis and 53 healthy controls were enrolled. Serum mannose-binding lectin levels were obtained by enzyme-linked immunosorbent assay (ELISA) using the mannose-binding lectin oligomer ELISA kit. Mannose-binding lectin 2 genotyping was performed by isolating the genomic DNA from leukocytes.
Mean mannose-binding lectin levels were 1693.2 and 1887.8 in the patient and control group, respectively. Although mannose-binding lectin levels were lower in the patient group, the difference was not statistically significant (P > .05). No overall association was observed between the mannose-binding lectin genotype and susceptibility to nasal polyposis (95% confidence interval = 0.716-4.389, odds ratio = 1.773). The mutant allele frequencies of the 3 structural polymorphisms did not differ significantly between the nasal polyposis patients and the controls (P = .659).
Mannose-binding lectins are not involved in the pathogenesis of nasal polyposis in adult Turkish patients, but additional research is needed for further comment.
Otolaryngology Head and Neck Surgery 02/2012; 147(1):79-84. · 1.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Sex chromosome abnormalities (SCAs) are the most common genetic disorder with a frequency of 1/400 or 1/500 live births. In this study we aimed to evaluate the initial indications, frequencies, and pregnancy termination rates of pregnancies with SCAs referred to Ege University Medical Faculty, Department of Medical Genetics. Prenatal diagnosis was performed in 7505 cases in the period of January 1998 through December 2009.
In this study, their initial indications and fetal karyotype results were evaluated retrospectively. A total of 60 pregnancies (0.80%) with SCA were evaluated. Turner syndrome was the most commonly diagnosed SCA in prenatal diagnosis (60%). The most common referral reason for pregnancies with Turner syndrome was cystic hygroma on ultrasonography. Of 14 pregnancies having a prenatal diagnosis with SCA (Turner syndrome: 7, Klinefelter syndrome: 5, Mosaic Turner syndrome: 2), 12 with SCA (85.7%) were terminated. The ratio of SCA in the prenatally diagnosed cases was similar to those reported in the literature. Although the ratio of terminated pregnancies with Turner syndrome was similar to those reported from European countries, all the pregnancies with Klinefelter syndrome have chosen termination, which showed a regional difference in Turkey.
It is important to consider the decisions of the families during the genetic counseling sessions of the couples having SCAs.
Genetic Testing and Molecular Biomarkers 02/2012; 16(2):150-3. · 1.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the genotoxic effects of (90)Y and (186)Re in patients with hemophilia who were undergoing radionuclide synovectomy (RS) procedure in the last 3 years.
Nineteen patients were enrolled in the study. Most of the patients (n = 17) were hemophilia-A (mean age 20.6 ± 10.5 years) and 18 patients (mean age 22.6 ± 10.6 years) with hemophilia who were not exposed to RS procedure were included in the study as control group. Most cases in the control group (n = 13) were hemophilia-A. (90)Y for knee joints and (186)Re for elbow or ankle joints were used to perform RS in hemophilic patients. We studied the micronucleus (MN) test on peripheral blood lymphocytes as an indicator of radiation-induced cytogenetic damage and calculated nuclear division index.
There was no significant difference between the patients with and without RS with respect to MN values. However, both values obtained in RS-exposed patients and control group were much elevated than values reported in literature from healthy controls. The mean MN values of patients below 20 years old were much lower but not significant than those above 20 years old. MN frequencies between (186)Re and (90)Y groups were also analyzed, and no significant difference was observed. Hemophilia patients who were treated with (186)Re showed higher levels of MN compared to patients treated with (90)Y although the difference was not significant.
Radioisotope synovectomy (RS) seems to be a safe procedure not causing a significant genotoxic effect on hemophilic patients, however, further studies including larger series of patients are needed to better understand the effects of RS on patients' health.
Annals of Nuclear Medicine 01/2012; 26(1):41-6. · 1.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Abstract Gaucher disease (GD) is the most frequent autosomal recessive lysosomal glycolipid storage disorder characterized by a decreased lysosomal activity of the enzyme β-glucocerebrosidase (GBA; EC 3.2.1.45). The aim of this study was to evaluate the spectrum of the GBA gene mutations in Turkish GD patients and to explore genotype/phenotype associations. The molecular characterization of 32 unrelated Turkish GD patients with three types of the disease was defined. Mutation analysis identified 96.9% of the GD alleles. The N370S mutation had the highest prevalence (50%) followed by the L444P (35.5%) alleles. We identified a novel L385R missense mutation that is associated with type 1 GD.
Journal of pediatric endocrinology & metabolism: JPEM 01/2012; 25(9-10):957-62. · 0.88 Impact Factor
-
International journal of dermatology 11/2011; 50(11):1406-10. · 1.18 Impact Factor
-
Emin Karaca,
Burak Durmaz,
Huseyin Aktug,
Huseyin Altug,
Teoman Yildiz,
Candan Guducu,
Melis Irgi,
Mehtap Gulcihan Cinar Koksal,
Ferda Ozkinay,
Cumhur Gunduz,
Ozgur Cogulu
[show abstract]
[hide abstract]
ABSTRACT: Concerns about the health effects of radiofrequency (RF) waves have been raised because of the gradual increase in usage of cell phones, and there are scientific questions and debates about the safety of those instruments in daily life. The aim of this study is to evaluate the genotoxic effects of RF waves in an experimental brain cell culture model. Brain cell cultures of the mice were exposed to 10.715 GHz with specific absorbtion rate (SAR) 0.725 W/kG signals for 6 h in 3 days at 25°C to check for the changes in the micronucleus (MNi) assay and in the expression of 11 proapoptotic and antiapoptotic genes. It was found that MNi rate increased 11-fold and STAT3 expression decreased 7-fold in the cell cultures which were exposed to RF. Cell phones which spread RF may damage DNA and change gene expression in brain cells.
Journal of Neuro-Oncology 07/2011; 106(1):53-8. · 3.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We assessed the association between interleukin-10 (IL-10) -1082G/A and -592C/A polymorphisms, and coronary heart disease (CHD).
A cross-sectional, observational study included 86 patients (mean age 43.36±4.930 years) diagnosed to have CHD and 88 healthy controls (mean age 47.07±8.135 years). IL-10 -1082G/A and -592C/A polymorphisms were analyzed using restriction fragment length polymorphism (RFLP) and agarose gel electrophoresis methods in both patient and control groups. Genotype distributions of the polymorphisms between CHD patients and controls were assessed by Chi-square analysis.
The genotype distribution of the -1082 G/A polymorphism was not different in premature CHD patients (GG: 38.3%; GA: 51.1%; AA: 10.6%) and controls (GG: 43.1%; GC: 43.1%; CC: 13.8%) (p=0.57). The prevalence of the A allele at -1082G/A polymorphism was 36.6% in patients and 35.3% in controls. Both allele and genotype frequencies of -592C/A polymorphism did not also differ significantly between patients with CHD and controls. We did not observe relationships between polymorphism-specific haplotypes and adverse angiographic and clinical outcomes. We have observed a significant difference of IL-10 -592C/A allelic frequency (OR=2.00 95% CI=0.9434-4.2579) between the younger CHD patients (<45 years, Group 2) and matched controls.
Our study suggests that IL-10-592C/A polymorphism may play a role in susceptibility to CHD in younger patients.
Anadolu kardiyoloji dergisi: AKD = the Anatolian journal of cardiology 06/2011; 11(4):285-9. · 0.44 Impact Factor
-
Ozgur Cogulu,
Ferda Ozkinay,
Haluk Akin,
Huseyin Onay, Emin Karaca,
Asude Alpman Durmaz,
Burak Durmaz,
Ayca Aykut,
Erhan Pariltay,
Ozgur Kirbiyik,
Cumhur Gunduz,
Cihangir Ozkinay
[show abstract]
[hide abstract]
ABSTRACT: A limited numbers of published studies evaluate the referral reasons for genetic counseling services in the literature. These studies are focused on prenatal genetic counseling services, in particular, prenatal diagnosis. In order to provide the most effective and helpful genetic counseling services, genetics professionals need adequate knowledge about the profile of individuals referred for these services. In addition, physicians need increased awareness of the nature of genetic issues in order to make appropriate referrals. This study was intended to provide a descriptive analysis of the referral reasons of patients that received genetic counseling at a genetics center in Izmir, Turkey during an 11-year period. A total of 8965 records generated between 1998 and 2008 from one genetic center (which consists of The Department of Medical Genetics and Division of Pediatric Genetics) were evaluated retrospectively. Of these, 6,258 involved referrals for prenatal reasons, and 2,707 involved referrals for postnatal reasons. Both prenatal and postnatal records were further classified into more specific categories of referral reasons. The most common reason for genetic counseling among the prenatal patients was advanced maternal age (42.0%), followed by high risk results on prenatal biochemical screening tests such as second trimester double test [(serum concentration of alphafetoprotein (AFP), beta-human chorionic gonadotropin (beta-HCG)], triple test (serum concentration of AFP, beta-HCG, oestriol) and integrated test (26.5%). The most common indications for postnatal patients were recurrent miscarriages (28.2%) and infertility (19.7%). A significant increase in number of specific categories of referrals for genetic counseling was observed for the last 3 years after the establishment of the Medical Genetics Department. These data provide useful information about the frequency of referrals to the genetics department, and the feasibility of genetic services. Organization of genetic services and systematic procedures for genetic counseling and genetic testing may improve the public's awareness of genetics and ensure a high standard of patient care.
Journal of Genetic Counseling 01/2011; 20(3):287-93. · 1.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Severe combined immunodeficiencies (SCID) comprise a spectrum of genetic defects that involve both humoral and cellular immunities. Defects in recombinating activating gene 1 (RAG1), RAG2, Artemis, or LIG4 can disrupt V(D)J recombination. Defective V(D)J recombination of the T and B cell receptors is responsible for T(-)B(-)NK(+)SCID. Amorphic mutations in RAG1 and RAG2 cause T(-)B(-)NK(+)SCID, whereas hypomorphic mutations cause an immunodeficency characterized by oligoclonal expansion of TCRgammadelta T cells, severe CMV infection and autoimmunity. First patient is a typical T(-)B(-)NK(+)SCID with clinical and immunologic findings while the second is atypical with normal immunoglobulin levels, CD4 lymphopenia, elevated TCRgammadelta T cells, persistent CMV infection, and autoimmune hemolytic anemia. These cases are presented to emphasize that mutations in RAG1 gene may lead to a diverse spectrum of clinical and immunologic findings while hypomorphic mutations may be related with autoimmunity and refractory CMV infection during infancy.
Clinical and Experimental Medicine 06/2009; 9(4):339-42. · 1.58 Impact Factor
-
Acta oncologica (Stockholm, Sweden) 05/2008; 47(8):1604-6. · 2.27 Impact Factor
-
Figen Tarhan,
Filiz Vural,
Buket Kosova,
Kenan Aksu,
Ozgur Cogulu,
Gokhan Keser,
Cumhur Gündüz,
Murat Tombuloglu,
Gonca Oder, Emin Karaca,
Eker Doganavsargil
[show abstract]
[hide abstract]
ABSTRACT: Telomerase is a reverse transcriptase enzyme contributing to the maintenance of the telomeric structure by adding telomere repeat sequences to chromosomal ends, thus compensating for its shortening. Telomerase activity which is common in cancers and human germ line tissue, may also be increased, although to a lesser extent, in systemic autoimmune diseases. We aimed to evaluate telomerase activity in a group of Turkish patients with various connective tissue diseases. In this cross sectional study, 19 patients with systemic sclerosis (SSc), 15 with systemic lupus erythematosus (SLE), 10 with rheumatoid arthritis (RA) and 14 with primary Sjögren's syndrome (pSjS) were studied. As the control group, 29 healthy subjects were also included. Human telomerase-specific reverse transcriptase (hTERT) was measured in peripheral blood lymphocytes, using online real-time reverse-transcriptase polymerase chain reaction (PCR). We also investigated if hTERT values in each patient group were correlated with clinical parameters and disease activity. Highest hTERT values were observed in RA group (21.24 +/- 28.54), followed by SLE (13.38 +/- 26.05) and pSjS (11.73 +/- 10.59) groups. Only hTERT values in RA group was significantly higher than the healthy control group (7.62 +/- 4.21) (p < 0.05). Interestingly, hTERT values in SSc were very low (2.09 +/- 3.18), even less than the healthy control group. In consistent with previous studies, telomerase activity was increased in SLE and RA. Very low telomerase activity in SSc group was rather surprising. Since existing telomerase data in SSc was limited and telomere shortening was previously reported in SSc, our finding of low telomerase activity in SSc group deserves relevant discussion and further studies.
Rheumatology International 05/2008; 28(6):579-83. · 1.88 Impact Factor
-
Ozgur Cogulu,
Buket Kosova,
Cumhur Gunduz, Emin Karaca,
Serap Aksoylar,
Ayse Erbay,
Deniz Karapinar,
Canan Vergin,
Filiz Vural,
Murat Tombuloglu,
Nazan Cetingul,
Ferda Ozkinay
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study is to evaluate (1) the human telomerase-specific reverse transcriptase (hTERT) mRNA expression in childhood acute leukemia, (2) the association between the hTERT mRNA expression with the patients' characteristics and the known prognostic factors and (3) the correlation of the patients' survival with the initial hTERT mRNA value at diagnosis. A total of 40 newly diagnosed patients consist of children [31 cases with acute lymphoblastic leukemia (ALL) and 9 cases with acute myeloblastic leukemia (AML)] were prospectively included into the study. The online real-time reverse-transcriptase PCR was used for the quantification of hTERT in bone marrow (BM). All cases were re-evaluated for their survival after 2 years. The highest hTERT mRNA value was observed in Pre B-cell ALL patients followed by B-cell ALL, T-cell ALL and AML. The hTERT mRNA relative ratio difference between the ALL and AML groups was significant. No significant association was found when hTERT mRNA expression was evaluated in relation with the hematological parameters (except hemoglobin level), blast percentages and the risk groups. No significant difference was determined between the rate of complete remission and relapse of cases with the hTERT mRNA values in all malignancy groups. Patients who had higher initial hTERT mRNA values showed significantly longer disease-free survival (DFS) and overall survival (OS) in ALL (P = 0.000 and 0.01, respectively). Although DFS and OS was longer in AML patients with lower initial hTERT mRNA, the difference was not significant. In conclusion, the hTERT mRNA expression values were not significantly associated with the known prognostic factors in children both with ALL and AML. hTERT mRNA value is a significant factor for childhood ALL at diagnosis in relation to the estimated survival.
International Journal of Hematology 05/2008; 87(3):276-83. · 1.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The objective of this study was to evaluate the incidence and reasons for referrals for prenatally detected Turner syndrome and cystic hygroma cases among prenatal cases performed between 1998 and 2007.
In this study 3,595 amniocentesis, chorionic villus and cordocenthesis materials obtained between 1998 and 2007 were evaluated. Among prenatal cases, 23 Turner syndrome cases were also evaluated according to their referral reasons. Among the indications of prenatal cases, cystic hygroma was evaluated according to karyotype results.
Twenty-three cases were Turner Syndrome in which 7 cases were detected to have mosaic pattern. The indications for prenatal diagnosis for the cases were cystic hygroma in 11 cases, missed abortion in 6 cases, advanced maternal age in 5 cases and positive screening test results in 1 case. Among 18 cases having cystic hygroma detected by ultrasonography, 8 cases (44.4%) were found to have a 45,X karyotype, 3 cases were found to be mosaic Turner syndrome (16.7%), 5 cases (27.7%) had normal karyotype, 1 case (5.6%) 47,XX,+13 and 1 case (5.6%) 47,XX,+21.
The present study indicates the importance of cystic hygroma in prenatal diagnosis of Turner Syndrome and other aneuploidies.
Fetal Diagnosis and Therapy 04/2008; 25(1):58-61. · 1.05 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Chromosomal changes are necessary in determining the classification, prognosis and using the appropriate therapeutic regimen in acute leukemia. Isochromosomes are uncommon chromosome aberations in childhood acute lymphoblastic leukemia (ALL) and the effect of i(9q) is not well established. We present an 8-year-old male case of pre-B ALL who has an unusual course at diagnosis. He was hospitalized three times in three different hospitals and blastic cells disappeared after the first hospitalization following blood transfusion without chemotherapy. In the following two hospitalizations no blastic cell was observed and transfused with a pack of erythrocyte suspension each time. In the fourth hospitalization, bone marrow aspiration revealed L1 type of lymphoid blast cell infiltration. The remission was achieved on the 15th day of the induction therapy and he has been in remission for the last 6 months. This unusual presentation and early remission achieved by induction therapy in this patient may support the literature that isochromosome 9q has a favourable outcome in childhood ALL.
Leukemia Research 12/2006; 30(11):1461-3. · 2.92 Impact Factor
