[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.
Results: 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.
Conclusion: 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
Key Words: Chromosomal abnormalities, Cytogenetic abnormalities,
Pathology, Spontaneous abortion
Turk Patoloji Dergisi 01/2015; DOI:10.5146/tjpath.2015.01303
[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.
[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.
Balkan Journal of Medical Genetics 06/2011; 14(1):25-30. DOI:10.2478/v10034-011-0014-3 · 0.17 Impact Factor
[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.
Cancer genetics and cytogenetics 12/2010; 203(2):230-7. DOI:10.1016/j.cancergencyto.2010.07.125 · 1.93 Impact Factor
[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.
Cancer Investigation 10/2010; 29(1):73-7. DOI:10.3109/07357907.2010.512599 · 2.06 Impact Factor
[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.
Turkiye Klinikleri Journal of Medical Sciences 05/2010; 30(6):1891-95. DOI:10.5336/medsci.2009-15088 · 0.10 Impact Factor
[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.
Human Mutation 10/2007; 28(10):1014-9. DOI:10.1002/humu.20556 · 5.05 Impact Factor
[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.
Balkan Journal of Medical Genetics 04/2007; 10(1):25-28. DOI:10.2478/v10034-007-0004-7 · 0.17 Impact Factor
[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.
The Turkish journal of pediatrics 01/2007; 49(3):322-6. · 0.56 Impact Factor
[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.
[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.
[Show abstract][Hide abstract] ABSTRACT: Until recently, presence of de novo marker or derivative chromosomes was quite problematic for genetic counseling especially in prenatal diagnosis, because characterization of marker and derivative chromosomes by conventional cytogenetic techniques was nearly impossible. However, recently developed molecular cytogenetic technique named Multicolor Fluorescence in Situ Hybridization (M-FISH) which paints all human chromosomes in 24 different colors allows us to characterize marker and derivative chromosomes in a single hybridization. In this study, we applied M-FISH to determine the origin of 3 marker and 3 derivative chromosomes. Marker chromosomes were found to originate from chromosome 15 in two postnatal and one prenatal case. Of these, one of the postnatal cases displayed clinical findings of inv dup (115) syndrome and the other of infertility, and the prenatal case went through amniocentesis due to the triple test results. Karyotypes of the patients with derivative chromosomes were designated as 46,XY,der (21)t(1;21)(q32;p11), 46,XX,der(8)t(8;9)(p23;p22) and 46,XX,der(18)t(18;20)(q32;p11.2) according to cytogenetic and M-FISH studies. All of the M-FISH results were confirmed with locus specific or whole chromosome painting probes. The case with der (8)t(8;9) had trisomy 9(p22-pter) and monosomy 8(p23-pter) due to this derivative chromosome. The case with der(18)t(18;20) had trisomy 20(p11.2-pter) and monosomy 18(q32-qter). Parental origins of the derivative chromosomes were analyzed using microsatellite markers located in the trisomic chromosomal segments. Patients' clinical findings were compared with the literature.
[Show abstract][Hide abstract] ABSTRACT: A case with de novo interstitial deletion of chromosome 7q21.1-q22: A patient with multiple congenital anomalies was found to have a de novo proximal interstitial deletion of chromosome 7q21.1-q22. The patient was 10.5 years of age, and manifestations include growth retardation (below 3rd percentile), mental retardation, mild microcephaly, hypersensitivity to noise, mild spasticity, short palpebral fissures, alternant exotropia, compensated hypermetropic astigmatism, hypotelorism, hypoplastic labia majora and minora, clinodactyly of fingers 4 and 5. Molecular studies revealed that the deletion had a paternal origin, while chromosomes of both parents cytogenetically were shown to be normal. Molecular, and fluorescence in situ hybridization (FISH) analyses confirmed no deletion at the Williams-Beuren Syndrome region. Some of the heterogeneous clinical findings were consistent with previously reported cases of same chromosomal breakpoints.
[Show abstract][Hide abstract] ABSTRACT: To assess the trends in the frequency and the medical effects of consanguinity in the south coast of Turkish population using local and national data in the last 11 years. This cross-sectional study was carried out in Manavgat province, which is a major tourism center on the Mediterranean coast of Turkey. The authors studied consanguineous marriages in rural and urban population in the Mediterranean coast, Manavgat province, Turkey, via a 1500 random survey sample of married couples. There has been a significant increase in the incidence of consanguineous marriages in rural areas (40.7%) since 1989 in the southern population of Turkey. The results showed that the most frequent type of marriage was between the first cousins. It is found that there is no statistically significant difference between the consanguineous and non-consanguineous marriages in the different age groups. The results were discussed on the basis of educational status, reasons for having consanguineous marriages and the general medical effects as well as with the relation of congenital malformations. The custom of consanguineous unions in the Mediterranean population of Turkey is still extremely high, and preventive measures should be done to decrease its frequency and associated complications.
Annales de Génétique 04/2004; 47(2):129-38. DOI:10.1016/j.anngen.2003.09.001
[Show abstract][Hide abstract] ABSTRACT: The RNASEL G1385A variant was recently found to be implicated in the development of prostate cancer. Considering the function of RNase L and the pleiotropic effects of mutations associated with cancer, we sought to investigate whether the RNASEL G1385A variant is a risk factor for breast cancer.
A total of 453 breast cancer patients and 382 age- and sex-matched controls from Greece and Turkey were analyzed. Genotyping for the RNASEL G1385A variant was performed using an Amplification Refractory Mutation System (ARMS).
Statistical evaluation of the RNASEL G1385A genotype distribution among breast cancer patients and controls revealed no significant association between the presence of the risk genotype and the occurrence of breast cancer.
Although an increasing number of studies report an association between the RNASEL G1385A variant and prostate cancer risk; this variant does not appear to be implicated in the development of breast cancer.
Anticancer research 01/2004; 24(4):2547-9. · 1.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Intervals V and VI of Yq11.23 regions contain responsible genes for spermatogenesis, and are named as "azoospermia factor locus" (AZF). Deletions in these genes are thought to be pathogenetically involved in some cases of male infertility associated with azoospermia or oligozoospermia. The aim of this study was to establish the prevalence of microdeletions on the Y chromosome in infertile Turkish males with azoospermia or oligozoospermia. We applied multiplex polymerase chain reaction (PCR) using several sequence-tagged site (STS) primer sets, in order to determine Y chromosome microdeletions. In this study, 61 infertile males were enrolled for the molecular AZF screening program. In this cohort, one infertile male had 46,XX karyotype and the remaining had 46,XY karyotypes. Forty-eight patients had a diagnosis of azoospermia and 13 had oligozoospermia. Microdeletions in AZFa, AZFb and AZFc (DAZ gene) regions were detected in two of the 60 (3.3%) idiopathic infertile males with normal karyotypes and a SRY translocation was determined on 46,XX male. Our findings suggest that genetic screening should be advised to infertile men before starting assisted reproductive treatments.
Annales de Génétique 01/2004; 47(1):61-8. DOI:10.1016/j.anngen.2003.09.002
[Show abstract][Hide abstract] ABSTRACT: ABSTRACT
Amniocentesis was performed at the 19th week of gestation because of advanced maternal age and a presumed risk of 1/14 for
Down syndrome as determined by the triple test. Chromosomal analysis of the fetus revealed a karyotype of 46,XX,inv(17)(p11.2;q25.1).
This chromosomal breakpoint can be associated with a microdeletion on chromosome 17 and be related with Smith-Magenis syndrome
and shown by cytogenetic observations. That is why, we have examined the fetus with the Smith-Magenis probe by the use of
fluorescence in situ hybridization (FISH) technique to identify the microdeletion of band p11.2 of chromosome 17. After it is confirmed
that the inverted chromosome is familial and no deletion has occurred, the pregnancy continued for a healthy carrier baby. These findings
have implications for prenatal counseling of carriers of pericentric inversions, who typically are considered to bear minimal reproductive
risk. This report shows that, FISH provides a reliable means for prenatal detection of the chromosome 17 rearrangements in this family.
Keywords: Chromosome 17, Pericentric inversion, Fluorescence in situ hybridization