[Show abstract][Hide abstract] ABSTRACT: Objective:
About 15% of clinically recognized pregnancies result in spontaneous abortion in the first trimester and the vast majority of these are the result of chromosome abnormalities. Studies of chromosomal constitutions of first trimester spontaneous abortions have revealed that at least 50% of the abortions have an abnormal karyotype. In this study we aimed to report the single centre experience of anomalies detected in spontaneous abortions.
Material and method:
We present rare numerical and structural cytogenetic abnormalities detected in spontaneous abortion materials and the histopathological findings of rest material of abortion specimens in our study population.
Among 457 cases, 382 were successfully karyotyped while cell culture of 75 cases failed. Cytogenetic abnormalities were detected in 127 of 382 cases (33.24%). Autosomal trisomies were the predominant chromosomal abnormalities with a frequency of 48.8%. Structural chromosomal abnormalities were infrequent in conception materials. The mean age of the mothers was highest in trisomy group, the difference being significantly important (ANOVA p < 0.001). The most frequent chromosomal abnormalities were Turner syndrome, triploidy and trisomy of chromosome 16 followed by trisomy of chromosomes 22 and 21 and tetraploidy. Double trisomies and structural chromosomal abnormalities were rare. Trisomies were more frequent in advanced maternal age.
Detection of chromosomal abnormalities in spontaneous abortion materials is very important to clarify the causes of loss of pregnancy. Detection of structural chromosomal abnormalities in the cases and their carrier parents can provide proper genetic counseling to these families. These families can be directed towards pre-implantation genetic diagnosis to prevent further pregnancies with complications.
Full-text · Article · May 2015 · Turk Patoloji Dergisi
[Show abstract][Hide abstract] ABSTRACT: Background
Fibroblast growth factor receptor 2 (FGFR2) mutations have been associated with the craniosynostotic conditions of Apert, Crouzon, Pfeiffer, Saethre-Chotzen, Jackson-Weiss, Beare-Stevenson Cutis Gyrata, and Antley-Bixler syndromes in various ethnic groups.
Thirty-three unrelated Turkish patients (12 Apert syndrome, 14 Crouzon syndrome, 6 Pfeiffer syndrome, and 1 Saethre-Chotzen syndrome) and 67 nonsyndromic craniosynostosis patients were screened for mutations in exons IIIa and IIIc of the FGFR2 gene by denaturing high-performance liquid chromatography and confirmed by direct sequencing.
We detected several pathogenic mutations in 11/33 (33%) patients with Apert syndrome (four with p.Pro253Arg; seven with p.Ser252Trp) and 8/33 (24%) patients with Crouzon syndrome (three with p.Trp290Arg, one with p.Cys342Tyr, p.Cys278Phe, p.Gln289Pro, and a novel p.Tyr340Asn mutation) and five patients (15%) with Pfeiffer syndrome (p.Cys342Arg, p.Pro253Arg, p.Trp290Arg, and p.Ser351Cys). No FGFR2 gene mutation was detected in any of the patients with Saethre-Chotzen syndrome and nonsyndromic craniosynostosis.
Our results indicate that the majority of Turkish patients with syndromic craniosynostosis have detectable genetic changes with an overall frequency of 72.7 percent. As this is the first molecular genetic report from a Turkish cohort, the identified spectrum profile of FGFR2 mutations of the syndromic craniosynostotic patients would be very helpful for understanding the genotype-phenotype relationship, and has a great value for diagnosis, prognosis, and genetic counseling.
Full-text · Article · May 2014 · Pediatric Neurology
[Show abstract][Hide abstract] ABSTRACT: Multiple pterygium syndrome is characterized by a number of phenotypic features, small stature, webbing of the neck, elbows, and/or knees, and joint contractures. In this report, we present an 11-year-old boy who had the classical findings of multiple pterygium syndrome, and his chromosomal analysis revealed a 47,XXY karyotype. Interestingly, he did not show any of the main clinical signs of Klinefelter syndrome. This patient appears to be the first reported case in the literature in which a non-mosaic 47,XXY karyotype has been found in a patient with multiple pterygium syndrome. The aim of the present report is to describe a non-classic Klinefelter syndrome associated with multiple pterygium syndrome and to emphasize the importance of karyotype analysis in patients with multiple pterygium syndrome.
No preview · Article · Sep 2013 · The Turkish journal of pediatrics
[Show abstract][Hide abstract] ABSTRACT: Objective: Cytoreductive surgery as a basis of therapy in epithelial ovarian carcinomas (EOC) provides the primary tumor and metastatic tumor samples from a same patient. This gives an excellent opportunity for evaluation of metastatic factors by excluding inter-individual differences. Therefore, we aimed to define changes at mRNA levels of NM23-H1, KAI1 and MKK4 metastasisrelated genes in the paired normal tissue, primary tumor and omental metastatic tumor samples obtained from a same patient. Material and Methods: mRNA levels were quantified by quantitative reverse transcription polymerase chain reaction (Q-RT-PCR) following total RNA extraction in normal tissues, primary malign tissues of EOC, and its metastatic lesions on omentum for 41 patients with stage III-C (FIGO) EOC. Results: We found that mRNA level of NM23-H1 was significantly higher in metastatic samples compared to primary tumors (p=0.009). On the other hand, MKK4 was found to be significantly lower in primary tumor samples compared to normal tissues (p=0.024). There was no significant change at mRNA level of KAI1 among normal tissues, primary tumors and omental metastatic tumor samples. Conclusion: We suppose that in detailed functional studies, approaches that suppress NM23-H1 gene and restore MKK4 gene would make these genes important molecular targets for treatment of metastatic EOC in the future.
No preview · Article · Aug 2012 · Turkiye Klinikleri Journal of Medical Sciences
[Show abstract][Hide abstract] ABSTRACT: Aim: To report a rare chromosomal abnormality, familial satellited Y chromosome (Yqs), in 3 Turkish prenatal cases. Material and methods: Metaphase chromosomes were prepared from amniocytes for prenatal cases and from lymphocytes for their fathers according to the standard methods. Results: In all cases, the analysis of all GTG-banded metaphases showed satellites on the long arms of chromosome Y as 46, XYqs karyotype. The indications for cytogenetic study were advanced maternal age and abnormal ultrasonographic findings with increased risk in the first trimester screening test. Cytogenetic studies of the fathers revealed that the Yqs were inherited. The satellites were positively stained by the silver-NOR technique, suggesting that the NORs were active for all cases. In accordance with the literature and the finding of paternal inheritance in all cases, genetic counselling was given to the families. The families decided to continue the pregnancies and all 3 babies were born at term without any dysmorphic features. Conclusion: Proper genetic counseling requires the accumulation of detailed information about the clinical follow-up evaluations and determination of whether the satellited Yqs is de novo or familial.
Full-text · Article · Oct 2011 · Turkish Journal of Medical Sciences
[Show abstract][Hide abstract] ABSTRACT: Approximately 30% of epileptic patients remain untreated, in spite of trials with maximum tolerable doses of more than one drug. The RalA binding protein 1 (RALBP1/RLIP76), a multifunctional, anti-apoptot-ic, multidrug transporter protein, has been proposed as being responsible for the drug resistance mechanism in epilepsy. We have investigated polymorphic differences in the coding regions and exonintron boundaries of the RLIP76 gene, between 146 refractory and 155 non refractory epileptic patients in Turkey, using denaturing high performance liquid chromatography (HPLC) and sequencing analysis techniques. We have detected the following sequence variants: c.160-4G>A, c.187C>G, c.1562-38G>A, c.1670+107G>A, c.1670+93G>A, c.1670+96G>A, c.1670+100C>T, c.1670+130C>T, c.1670+131G>C, c.1670+140 G>C, and found no statistically significant correlation between allele frequencies and drug response status. We conclude that sequence variants of this gene are not involved in drug resistance in epilepsy.
Full-text · Article · Jun 2011 · Balkan Journal of Medical Genetics
[Show abstract][Hide abstract] ABSTRACT: Distribution and prevalence of germline mutations in BRCA1 and BRCA2 differ among different populations. For the Turkish population, several studies have addressed high-risk breast cancer and ovarian cancer (BC-OC) patients. In most studies, both genes were analyzed in part, and a quite heterogeneous mutation spectrum was observed. For high-risk Turkish prostate cancer (PCa) patients, however, there are no data available about mutations of germline BRCA genes. To accurately determine the contribution of germline mutations in BRCA1 and BRCA2 in Turkish BC, OC, and PCa high-risk patients, 106 high-risk BC-OC patients, 50 high-risk PCa patients, and 50 control subjects were recruited. The study represents the only full screening, to date, of a large series of Turkish high-risk BC-OC patients and the only study in Turkish high-risk PCa patients. Mutation screenings were performed on coding exons of both genes with either denaturing gradient gel electrophoresis or denaturing high performance liquid chromatography, or with both techniques. Three deleterious mutations in BRCA1 and three deleterious mutations in BRCA2 were detected in different BC-OC patients, and one truncating mutation was detected in a high-risk PCa patient. In addition, 28 different unclassified and mostly novel variants were detected in both genes, as well as several silent polymorphisms. These findings reflect the genetic heterogeneity of the Turkish population and are relevant to genetic counseling and clinical management.
No preview · Article · Dec 2010 · Cancer genetics and cytogenetics
[Show abstract][Hide abstract] ABSTRACT: In this study, MLPA assay was performed for detection of large rearrangements of BRCA1 and BRCA2 genes in 16 familial, 29 early onset, 3 male breast cancer, and 2 bilateral breast/ovarian cancer high risk Turkish index cases. MLPA assay for all exons of both genes and for 1100delC variant of CHEK2 gene were performed. Analyses, revealed no large genomic rearrangements in both genes, and, no 1100del variant in CHEK2 gene. Our data which represents the first results for Turkish patients, suggest that, the frequency of BRCA1 and BRCA2 genes' large rearrangements is very low.
No preview · Article · Oct 2010 · Cancer Investigation
[Show abstract][Hide abstract] ABSTRACT: Objective: The aim of this study was to determine the prevalence of the HFE gene mutations (C282Y, S65C and H63D) in patients with cryptogenic cirrhosis and, hemochromatosis and healthy control individuals. Material and Methods: The exon 2 and exon 4 of the HFE gene were amplified by polymerase chain reaction (PCR) in the DNA samples of 18 cryptogenic cirrhotic and 11 hemochromatosis patients, and 141 healthy control individuals.Then the restriction fragment length polymorphism (RFLP) method was used to detect the mutations. Results: The frequencies of C282Y, S65C and H63D mutations were found as 0.0, 0.0, 0.12 in healthy Turkish population and 0.0, 0.0, and 0.11 in cryptogenic cirrhotic patients, respectively. We also screened 11 hemochromatosis patients for these mutations, and the frequencies of the mutations were found as 0.0 for C282Y, 0.0 for S65C, and 0.27 for H63D mutation. There was no difference between the control group and cryptogenic cirrhosis group. However, we found differences in the frequency of the H63D mutation between the control group and hemochromatosis group. Conclusion: The frequencies of the C282Y and S65C mutations were found as 0.0 in Turkish population and in the patients with cryptogenic cirrhosis such as in the other Asian populations. However, the frequency of the H63D mutation was higher than previously reported Asian populations. These results suggest that the H63D mutation may be responsible for the hereditary hemochromatosis in Turkish population.
Full-text · Article · May 2010 · Turkiye Klinikleri Journal of Medical Sciences
[Show abstract][Hide abstract] ABSTRACT: Aplasia cutis congenita (ACC) is an uncommon condition in which localized or widespread areas of skin are absent or scarred at birth. There is no single underlying cause of ACC, as it simply represents a physical finding that reflects a disruption of intrauterine skin development. Here we report three cases of ACC of the scalp with three different etiologies: congenital rubella syndrome, trisomy 13 and fetal valproate syndrome. The aim of the present report is to increase awareness of these skin defects and emphasize the importance of underlying etiologies.
Full-text · Article · Sep 2009 · The Turkish journal of pediatrics
[Show abstract][Hide abstract] ABSTRACT: Subtelomeric rearrangements are an important cause of both sporadic and familial idiopathic mental retardation (MR) and/or congenital malformation syndromes. We report on a cohort of 107 children with idiopathic MR and normal karyotype 450-550 band level by GTG banding screened for subtelomeric rearrangements by multiprobe fluorescence in situ hybridization (FISH). In these cases, five patients had de novo deletions (1p deletion was found in 2 cases; 3q deletion, 9p and 9q deletions were found in 1 case each) and four patients had unbalanced rearrangements [der(5)t(5;15)(pter;qter)pat in 2 patients who were siblings, rec(10)dup(10p)inv(10)(p13q26)mat in 1 patient and der(18)t(18;22)(qter;qter) de novo in 1 patient]. Our study confirms that the subtelomeric rearrangements are a significant cause of idiopathic MR with dysmorphic features.
Full-text · Article · Sep 2009 · The Turkish journal of pediatrics
[Show abstract][Hide abstract] ABSTRACT: Prenatal diagnosis of a de novo supernumerary marker chromosome originating from chromosome 16: A 37 year old pregnant woman was referred for amniocentesis at 18 weeks of gestation due to advanced maternal age and abnormal serum biochemistry. A nonsatellited, monocentric marker chromosome was observed with a frequency of 57% in cultured amniocytes. Parental karyotypes were normal. The marker chromosome was found to be derived from chromosome 16 by FISH using CEP16 and WCP16 probes. Marker chromosomes were not painted with M-FISH probe mixture, indicating an exclusively heterochromatin nature. CGH analysis using genomic DNA isolated from uncultured amniocytes also supported the M-FISH results. Genetic counseling was given to parents and the family decided to continue the pregnancy to term. The baby was born at 36 weeks of gestation without any dysmorphic features. Follow-up at 7 months of age revealed no developmental abnormalities.
[Show abstract][Hide abstract] ABSTRACT: Human MYO15A is located on chromosome 17p11.2, has 66 exons and encodes unconventional myosin XVA. Recessive mutations of MYO15A are associated with profound, nonsyndromic hearing loss DFNB3 in humans, and deafness and circling behavior in shaker 2 mice. In the inner ear, this motor protein is necessary for the development of hair cell stereocilia, which are actin-filled projections on the apical surface and the site of mechanotransduction of sound. The longest isoform of myosin XVA has 3,530 amino acid residues. Two isoform classes of MYO15A are distinguished by the presence or absence of 1,203 residues preceding the motor domain encoded by alternatively-spliced exon 2. It is not known whether this large N-terminal extension of myosin XVA is functionally necessary for hearing. We ascertained approximately 600 consanguineous families segregating hereditary hearing loss as a recessive trait and found evidence of linkage of markers at the DFNB3 locus to hearing loss in 38 of these families ascertained in Pakistan (n=30), India (n=6), and Turkey (n=2). In this study, we describe 16 novel recessive mutations of MYO15A associated with severe to profound hearing loss segregating in 20 of these DFNB3-linked families. Importantly, two homozygous mutant alleles-c.3313G>T (p.E1105X) and c.3334delG (p.G1112fsX1124) of MYO15A-located in exon 2 are associated with severe to profound hearing loss segregating in two families. These data demonstrate that isoform 1, containing the large N-terminal extension, is also necessary for normal hearing.
[Show abstract][Hide abstract] ABSTRACT: Hemochromatosis gene (HFE) mutations are associated with hereditary hemochromatosis. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to determine the frequency of the mutations (C282Y, S65C and H63D) of the HFE gene in DNA samples of 141 healthy Turkish adults in Antalya, Turkey. The mutant allele frequencies were 0.0, 0.0 and 0.12, respectively. The H63D mutation was found in the heterozygous state in 30 samples (21.27%) and in the homozygous state in two samples (1.41%). These results suggest that the H63D mutation may be responsible for the hereditary hemochromatosis in the Turkish population.
Full-text · Article · Apr 2007 · Balkan Journal of Medical Genetics
[Show abstract][Hide abstract] ABSTRACT: We report a newborn girl with multiple congenital anomalies whose chromosomal analysis showed complete trisomy 22. Her phenotype included microcephaly, epicanthus, hypertelorism, micrognathia, cleft palate, microtia, and preauricular tag. She died in the 24th post-natal hour. Trisomy 22 was shown by fluorescence in situ hybridization technique and the parental origin of the extra chromosome was found to be maternal by DNA microsatellite marker analysis of chromosome 22. Postmortem examination revealed the presence of atrioseptal defect and stasis in the biliary canals. We believe that this patient will contribute to the literature both by clinical findings and short life span associated with maternal origin of extra chromosome 22.
Full-text · Article · Jan 2007 · The Turkish journal of pediatrics
[Show abstract][Hide abstract] ABSTRACT: To evaluate both women's and their spouses' reasons for undergoing amniocentesis, their concerns relating to the procedure as well as their psychological reactions and coping mechanisms during the testing period.
Eighty-five women undergoing amniocentesis and their spouses took part in the study. The couples completed a questionnaire that provided demographic data and insights into their experiences of amniocentesis.
Age was the main reason for undergoing amniocentesis. When they first learned that they were going to undergo amniocentesis, women were more concerned about the potential danger to their fetus than their spouses. Most of participants believed that their pregnancy would continue after amniocentesis. However, they also stated that they were prepared for an abortion. Uncertainty and tension were two significant emotions experienced by couples while waiting for the test results. For the majority of women (80%) and men (42.3%) the strongest support was provided by their spouses during this period. In summary, we can conclude that the test did have a major psychological impact on both women and their spouses, but did not have a negative impact on their coping mechanisms.
The psychological impact of amniocentesis on women and their spouses does not constitute a major obstacle to their ability to cope. However, a certain number of couples reported feelings of uncertainty, tension and anxiety about fetal injury. We strongly suggest that counseling should be given to high-risk families and that prenatal/antenatal care units must be established.
No preview · Article · Apr 2006 · Journal of Psychosomatic Obstetrics & Gynecology
[Show abstract][Hide abstract] ABSTRACT: Beta-thalassemia, which is an autosomal recessive disease, is among the most common hemoglobinopathies in Antalya, Turkey. Mutations found in Turkish beta-thalassemia patients constitute a heterogeneous group, which is mostly composed of point mutations and, only in very rare cases, a deletion or an insertion causes affected or carrier phenotypes. Reverse dot blot hybridization (RDBH) method is used for screening common mutations, and sequence analysis and silver staining were performed consecutively to detect any uncommon mutation. The authors report a first Turkish family with a rare variant--intervening sequence 2 (IVS2) 849 (A-G). The proband's mother and father were determined as carriers of IVS2.849 (A-G) and IVS1.1 (G-A) mutations, respectively. Proband is the first child of the family and she has an IVS2.849 (A-G)/IVS1.1 (G-A) genotype with ss-thalassemia major phenotype. Prenatal diagnosis was performed for the second child, and genotype of the fetus was determined as IVS2.849 (A-G)/Normal. This first report of IVS2.849 (A-G) mutation in Turkish population shows that there are many more mutations contributing the heterogeneity of the mutation spectrum of beta-globin gene in the Turkish population, which indicates migrations of different ethnic origins.
No preview · Article · Jul 2005 · Pediatric Hematology and Oncology
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: Invasive methods prenatal diagnosis has been recognized as a safe reliable method for couples at high risk of giving birth to child with clinically significant chromosomal abnormality or other genetic diagnosis. Chorionic villus sampling (CVS), amniocentesis (AS) and cordocentesis (KC) have been used as prenatal diagnosis techniques since 30 years. AS is performed 15 weeks gestation and is the most widely used invasive technique. CS is performed after 18 to 20 weeks of pregnancy and CVS may be carried out after 11 weeks. STUDY DESIGN: The most common indications are a raised risk of Down's syndrome and other trisomies, advanced maternal age triple testing pathological ultrasonographic findings. Prenatal karyotypes were undertaken in 2084 amniotic fluid samples, 122 CVS, and 199 CS. The frequency of fetal abnormal karyotypes were 2.95% (71/2405 cases). RESULT(s): Among the fetal abnormal karyotypes, the frequency of numerical chromosome abnormalities and structural chromosome abnormalities were 1.87% (45/71 cases) and 1.08% (26/71 cases), respectively. In the numerical abnormalities, the frequency of trisomy 21 was by far the highest (21/45 cases), followed by sex chromosome aneuploidies in 15 cases. In the structural chromosomal rearrangements, 2 cases had familial inversions chromosome 17 and Y. Chromosomal deletion in one case, duplication one case and extra marker chromosome in two cases were detected. The remaining 19 cases had translocation, 11 of them had reciprocal translocations and 8 cases had Robertsonian translocations. Among them, 13 cases had balanced translocation and 6 had unbalanced. Out of 19 cases with translocation carriers, sixteen cases were inherited from one of the parents and three cases were de now, genetic counceling was given for families.