Turgay Budak

FSHR Single Nucleotide Polymorphism Frequencies in Proven Fathers and Infertile Men in Southeast Turkey

The influence of FSH receptor (FSHR) variants on male infertility is not completely understood. The present investigation is the first screening study for SNP at nucleotide position −29 in the core promoter region and codon 680 in exon 10 of the FSHR and the effect of the serum levels of FSH on male infertility in Southeast Turkey. The SNPs in codon 680 and at position −29 of the FSHR gene were analyzed by PCR-RFLP technique in 240 men with proven fathers, and 270 infertile men (150 nonobstructive azoospermic and 120 severe oligozoospermic). The separate analysis for SNP at nucleotide position −29 did not show any difference in genotypic frequencies and serum FSH levels. The genotype distribution of SNP at position 680 was different but does not influence serum FSH levels. Together the two SNPs form four discrete haplotypes (A-Thr-Asn, G-Thr-Asn, A-Ala-Ser, and G-Ala-Ser) occurring in 10 combinations. A statistically significant difference in the allelic distribution of G-Asn/G-Ser and G-Ser/G-Ser genotype between proven fathers and infertile men but there were not any statistically significant difference in the overall frequency of the four FSHR haplotypes. We conclude that the FSHR haplotype does not associate with different serum FSH levels but it is differently distributed in proven fathers and infertile men.

Parental Decisions Regarding a Prenatally Detected Fetal Chromosomal Abnormality and the Impact of Genetic Counseling: An Analysis of 38 Cases with Aneuploidy in Southeast Turkey

This study investigated parental decision-making to terminate or continue a pregnancy after prenatal diagnosis of a chromosomal abnormality among a sample of patients in Southeast Turkey. Between 2004 and 2007, 1068 amniocentesis tests were performed in the Medical Biology and Genetic Department Laboratory at Dicle University. Aneuploidy was found in 38 cases (3.56%). Genetic counseling was provided for the couples that received abnormal results, and they were later interviewed and asked if they had continued or interrupted the pregnancy after the diagnosis. When confronted with autosomal aneuploidy in which a severe prognosis was expected, 85% of cases decided to terminate the pregnancy. When confronted with sex chromosome aneuploidy with a low risk of an abnormal clinical phenotype 60% of cases decided to continue the pregnancy. Among the diagnoses with aneuploidy, pregnancy was continued in 21.1% of cases due to religious beliefs regardless of whether there was a low or severe risk of an abnormal clinical phenotype. These findings indicate that both severity of abnormality and religiosity play an important role in genetic counseling patients’ decision-making processes and outcomes in Turkey. In addition, the findings suggest the need for legislation that reduces the differences in approaches between the physicians and institutions regarding parental decision-making to terminate or continue a pregnancy in our country.

Polymorphisms of the angiotensin converting enzyme and angiotensin II type 1 receptor genes and renal scarring in non-uropathic children with recurrent urinary tract infection

Aim:  The aim of this study was to investigate whether the angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (A1166C) gene polymorphisms were associated with the renal scar formation secondary to recurrent urinary tract infection in children without uropathy.

The lack of effect of therapeutic vaccination with a pre-S2/S HBV vaccine in the immune tolerant phase of chronic HBV infection.

Background/Aims Even if the results are controversial and preliminary, several reports suggest that the HBV vaccine might be effective in treating HBV infection. In this study, we aimed to evaluate the efficacy and safety of specific anti-HBV vaccination for the immune tolerance phase of chronic HBV infection in a randomized, controlled study. Patients and Methods The 47 subjects included patients that were treatment-naive with hepatitis B e antigen positivity, active hepatitis B virus replication as measured by hepatitis B virus DNA levels, persistently normal alanine transaminase levels, and with minimal or absent disease activity by liver biopsy. Thirty patients were given three intramuscular injections of 20 &mgr;g of a pre-S2/S vaccine (GenHevac-B) on days 0, 30, and 60, and the remaining 17 patients were included in the control group. The efficacy of vaccination was evaluated by testing for loss of serum HBV DNA or decrease in its level and for HBeAg seroconversion. A significant decrease in HBV DNA levels was accepted as a decrease of >50% of initial values. The complete response was defined as loss of HBV DNA in serum with HBeAg seroconversion. Postvaccination follow-up lasted 12 months after the first dose. Results No significant effects were observed in the vaccination population in the reduction of HBV DNA to undetectable levels, or to <50% of prevaccination levels, in HBeAg/anti-HBe seroconversion, or in transaminase levels. There was an early clearance/decrease in HBV DNA levels in five vaccinated patients by 3 months, and none in controls (P = 0.143), and two of them had sustained responses later. At the end of follow-up, complete response is almost similar in study as well as control group (13% vs. 12%, P > 0.05). Disappearance of serum HBV DNA was more frequently observed in those patients who had pretreatment viremia of <100 pg/mL in both groups. The median levels of HBV DNA and alanine transaminase activity between baseline and 12 months did not differ significantly in both groups. All patients remained HBsAg positive and none developed anti-HBs. No serious adverse event was encountered in vaccinated patients, and the therapy was well tolerated. Follow-up lasted a median of 16 months (range 12–30 months) for the study group and 18 months (range 12–31months) for the control group. Conclusions Immunotherapy with specific anti-HBV vaccine in the immune tolerance phase of chronic HBV infection did not offer additional benefit. New immunotherapeutic strategies to control HBV infection by specific HBV vaccines in chronically infected subjects are needed.

Tetrasomy 18p in a male dysmorphic child in southeast Turkey

Small supernumerary chromosomes (sSMC) of an unknown origin are commonly referred to as ‘marker chromosomes’ or ‘ESACs’ (extra structurally abnormal chromosomes) (Blennow et al. 1993; Pietrzak et al. 2007). They are found in an about 0.043% of the human population and have been estimated to result in an abnormal phenotype approximately 30% of sSMC carriers (Pietrzak et al. 2007). Isochromosomes are supernumerary marker chromosomes, that are made up of two copies of the same arm of a chromosome, so that they form a mirror image of each other, resulting in a tetrasomy of the arm involved (Boyle et al. 2001; Ramegowda et al. 2006). Prevalence of various kinds of isochromosomes range from 0.14 to 0.72 per 1000 live births (Boyle et al. 2001; Ramegowda et al. 2006). The presence of a supernumerary isochromosome 18p results in tetrasomy of 18p (Boyle et al. 2001; Bakshi et al. 2006; Ramegowda et al. 2006). Tetrasomy of 18p is found one in every 140,000 live births, affecting males and females equally (Ramegowda et al. 2006). The tetrasomy 18p syndrome most often expresses itself with moderate to severe mental impairment, very delayed speech, poor or nonexistent ability to self feed, much delayed ability to walk, microcephaly, a long, asymmetric face, low set or malformed ears, a small pinched nose, short palpebral fissures, a small jaw, and congenital heart diseases, etc. (Callen et al. 1990; Boyle et al. 2001; Bakshi et al. 2006; Ramegowda et al. 2006). The characterization of marker chromosomes by conventional cytogenetic methods can be difficult, and these methods allow only the first step of diagnosis of isochromosomes, whereas fluorescence in situ hybridization (FISH) is the most common, rapid and reliable technique used to delineate isochromosomes (Gocke et al. 1986; Callen et al. 1990; Ramegowda et al. 2006; Pietrzak et al. 2007).

Cytogenetic and clinical studies of a male infant with disorder of sexual development: case report

OBJECTIVE To report a translocation between chromosomes 3 and 4: 46,XY,t(3;4)(p25;q31.3) in a male infant with a disorder of sexual development. DESIGN Case report. SETTING University hospital. PATIENT(S) A 1-year-old infant who presented with abnormal location of the urethral meatus. INTERVENTION(S) Cytogenetic analysis, fluorescence in situ hybridization (FISH), and serum concentrations measurement (using peripheral blood), and clinical examination. MAIN OUTCOME MEASURE(S) Karyotype and clinical findings. RESULT(S) On clinical examination, bilateral testicular volume and phallus were determined to be undersized. Serum concentrations of T and DHEAS were low. G-banding of his chromosomes showed that the patient had a balanced translocation involving chromosomes 3 and 4: 46,XY,t(3;4)(p25;q31.3). This karyotype finding was confirmed by FISH. The FISH analysis revealed the presence of sex-determining region (SRY). The proband inherited this translocation from his father. His sister had the same translocation. However, the father and sister of the proband were clinically normal. CONCLUSION(S) The presence of this chromosomal anomaly and hypospadias was unique to our patient compared with others with the 46,XY,t(3;4) translocation. Although no such association has been reported to date, we think that the severe hypospadias in our case might be associated with this translocation.

Patau Sendromlu Bir Prenatal Tani Olgu Sunumu

The aim of this study was to determine the effect of carbamazepine onserum lipid levels in epileptic patients who were on long-termcarbamazepine monotherapy. The study group were comprised of 30epileptic patients (10 female, 20 male) who have been on carbamazepinemonotherapy for at least one year whereas control group consisted of 30 ageand sex matched healthy controls. Serum cholesterol (total cholesterol,HDL cholesterol, LDL cholesterol) and triglyceride levels were measuredand LDL/HDL ratio was calculated in all subjects. Serum HDL cholesteroland triglyceride levels of study group were significantly higher than controlgroup whereas serum LDL cholesterol levels and LDL/HDL ratios of studygroup were lower than control group. Mean total cholesterol level of studygroup was lower than control group, however the difference did not reachstatistical significance level. Because of its effect on cholesterol levels, longterm carbamazepine could possibly have a positive influence in decreasingthe risk of developing aterosclerosis and coronary heart disease. Long termprospective follow-up studies would be helpful to us in enlightening this issuedefinitely.

Different chromosome Y abnormalities in a case with short stature.

We report a case with different chromosome Y abnormalities. Case was an 11-year-old boy, who was diagnosed with short stature, referred to laboratory of human medical genetics laboratory for genetic evaluation. Chromosomal analysis of the case was carried out on peripheral blood lymphocyte culture. Classic cytogenetic analysis (G and C banding) was confirmed by using fluorescence in situ hybridization analysis (FISH) technique. Cytogenetic and FISH analysis showed a mosaic 46,X,i(Yq)/45,X/47,X,i(Yq)x2/47,XYY karyotype. Case, which was found interesting due to its rarity, is discussed with its clinical features and cytogenetic results, in the light of relevant source information. This case underlines the importance of karyotyping patients with unexplained short stature. This clinical report also will be helpful in defining the phenotypic range associated with these karyotypes.

A case of complete tetraploidy in amniocentesis with normal karyotype in subsequent cordocentesis

We report a case of complete tetraploidy in amniotic fluid culture obtained at 17 wk of pregnancy. Amniocentesis was performed in this pregnancy because of a high-risk maternal serum screening result and abnormal ultrasound findings. Amniotic fluid was cultured in two flasks. Growth was very slow in one culture with no growth in the other. Harvest was possible after 3 wk, which revealed tetraploidy in all studied plates. Subsequent cordocentesis was performed to confirm the diagnoses of amniocentesis. Chromosomal analysis of the cordocentesis revealed a normal karyotype with 46,XY. A healthy male infant was born at term. This case illustrates that abnormal karyotypes in poor growth cultures could be misleading and should be confirmed by another technique, such as cordocentesis.

Genetics Analysis with Down Syndrome and Histopathological Examination of Buccal Epithelial Cells

El sindrome de Down es causado principalmente por la trisomia del cromosoma 21. Se revisaron los estudios citogeneticos realizados en 1.048 pacientes que fueron remitidos a la Unidad de Citogenetica del Dicle University Hospital, Diyarbakir, sudeste de Turquia, entre los anos 2000 y 2009. Los casos se agruparon de acuerdo a la razon de referencia para el analisis citogenetico. Las frecuencias mas altas de cariotipos anormales se encontraron ent los casos que fueron remitidos por sospecha de sindrome de Down (84,8%). Para el estudio histologico de las personas con y sin sindrome de Down, se realizo el frotis de mucosa oral por hisopado. Los grupos con sindrome de Down y de control (sin sindrome) se compararon estadisticamente en relacion a las celulas epiteliales orales y los nucleos (p <0,05). Se observaron nucleos perifericos en algunos pacientes con sindrome de Down, mientras que estructuras de tipo brotes en la forma de micronucleos se observaron en las celulas carioliticas.