Tahsin Yakut

Novel TSHR mutations in consanguineous families with congenital nongoitrous hypothyroidism.

Objective  Nonsyndromic autosomal recessively inherited nongoitrous congenital hypothyroidism (CHNG) can be caused by mutations in TSHR, PAX8, TSHB and NKX2‐5. We aimed to investigate mutational frequencies of these genes and genotype/phenotype correlations in consanguineous families with CHNG.

GST (GSTM1, GSTT1, and GSTP1) polymorphisms in the genetic susceptibility of Turkish patients to cervical cancer

OBJECTIVE This work investigates the role of glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), and glutathione S-transferase P1 (GSTP1) enzymes and polymorphisms, which are found in phase II detoxification reactions in the development of cervical cancer. METHODS This study was conducted with 46 patients diagnosed with cervical cancer and 52 people with no cancer history. Multiplex PCR methods were used to evaluate the GSTM1 and GSTT1 gene polymorphism. However, the GSTP1 (Ile105Val) gene polymorphism was studied using a PCR-RFLP method. The patient and control groups were compared using a chi-square test with p<0.05. RESULTS In the patient group, statistical significance was determined for gravidity (p=0.03), parity (p=0.01), and the number of living children (p=0.01) compared to the control group. The gene frequency of GSTM1, GSTT1, and GSTP1 polymorphisms was evaluated. We observed that GSTM1 and GSTT1 null genotype frequencies were 54.3% and 32.6% respectively, while GSTP1 (Ile/Val), (Ile/Ile), (Val/Val) genotype frequencies were 52%, 44%, and 4%, respectively, in the cervical cancer patients. No statistical variation was determined between the control and patient groups in terms of GSTM1, GSTT1, and GSTP1 polymorphisms (p>0.05). CONCLUSION Our results demonstrate that GSTT1, GSTM1, and GSTP1 polymorphisms are not associated with cervical cancer in Turkish patients.

Lack of association of ACE gene I/D polymorphism with obstructive sleep apnea syndrome in Turkish patients

Angiotensin-converting enzyme (ACE) is a vital enzyme in the renin-angiotensin-aldosterone system, and there are reports in the literature describing its role in the development of cardiovascular system diseases, with I/D polymorphism of the ACE gene. We examined the relationship between a patient group with obstructive sleep apnea syndrome (OSAS) and a control group in terms of I/D polymorphism of the ACE gene. We examined 64 patients, with 37 individuals serving as the control group. PCR was used to detect ACE I/D gene polymorphism. Genotype was determined according to the bands that formed on agarose gel electrophoresis. Among the 64 OSAS patients, 27 were identified with the ID genotype, 27 with the DD genotype and 10 with the II genotype; among the 37 control subjects, 19 were identified with the ID genotype, 11 with the DD genotype and 7 with the II genotype. When the case group and controls were compared in terms of ID, II and DD genotypes, no significant difference was observed. On the other hand, when the two groups were compared with respect to mean body mass index, the OSAS group was found to be significantly different from the control group (P = 0.009). We conclude that ACE I/D gene polymorphism is not a genetic risk factor for OSAS in Turkish patients.

Esophageal atresia and tracheo-esophageal fistula in a patient with digeorge syndrome

DiGeorge Syndrome (DGS) is a congenital disorder that affects the thymus, parathyroid glands, and heart and brain. Thymus involvement in DGS may vary between absence/hypoplasia of thymus to various forms of reduced T cell function. TBX1 deficiency causes a number of distinct vascular and heart defects, suggesting multiple roles in cardiovascular development, specifically, formation and growth of the pharyngeal arch arteries, growth and septation of the outflow tract of the heart, interventricular septation, and conal alignment. Here the authors describe a case of DGS presenting with severe combined immunodeficiency, esophageal atresia, and tracheoesophageal fistula (TEF). DGS is an important differential diagnosis in TEF.

Investigation of ABCB1 gene polymorphism with colchicine response in Behçet's disease.

Colchicine is commonly used in the treatment of Behçets disease. However, some patients are unresponsive to colchicine treatment. Adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) transports colchicine out of cells. We investigated a possible association of C3435T polymorphism of the ABCB1 (MDR1) gene with colchicine response in patients with Behçets disease. We randomly selected 97 patients with Behçets disease, examined ABCB1 (MDR1) gene C3435T polymorphisms, and evaluated patient responses to colchicine. Forty-three patients were colchicine responsive, while the remaining 54 patients were unresponsive. No significant difference was found between genotypic and allelic frequencies of the ABCB1 C3435T polymorphisms in patients with Behçets disease and healthy volunteers. Also, there was no significant difference among responsive and nonresponsive patients. We concluded that ABCB1 C3435T polymorphism is not associated with a colchicine response in patients with Behçets disease.

XRCC1 Gene Polymorphisms and Risk of Lung Cancer in Turkish Patients

Abstract Polymorphisms in the X-ray repair cross complementing 1 (XRCC1) gene have been found to be associated with susceptibility to various types of cancers. We investigated the association between the XRCC1 gene Arg399Gln polymorphism and the susceptibility to lung cancer in Turkish patients. To determine the association of this polymorphism with the risk of lung cancer in Turkish patients, a hospital-based case-control study was designed, involving 67 patients with lung cancer and 60 control subjects with no cancer history who were matched for age and gender. XRCC1 genotypes (Arg/Arg, Arg/Gln, and Gln/Gln) were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis on genomic DNA. No statistically significant relationship was determined between the lung cancer and control groups (p>0.05). Among the patients, 61% were Arg/Arg, 28% were Arg/Gln, and 11% were Gln/Gln. Among the controls, 50% were Arg/Arg, 38% were Arg/Gln, and 12% were Gln/Gln. There was no difference in the distribution of XRCC1 genotypes or the frequencies of the Arg (75% versus 69%) and Gln (25% versus 31%) alleles between the lung cancer patients and controls. Our results suggest that the XRCC1 gene Arg399Gln polymorphism is not associated with an increased risk for the development of lung cancer in Turkish patients.

Meiotic segregation analysis of reciprocal translocations both in sperms and blastomeres

Balanced chromosomal rearrangements could lead to unbalanced segregation gametes during meiosis. In this study, sperm flourescence in situ hybridization (FISH) analysis of meiotic segregation products of four reciprocal translocations; 46,XY,t(7;10)(q21;q22), 46,XY,t(15;17)(q11;p12), 46,XY,t(6;13)(p21.1;q32), and 46,XY,t(1;13)(q24;q10) are presented. In three out of these four cases with t(15;17), t(6;13), and t(1;13) additional blastomere FISH analyses are also provided. Multi‐color FISH analysis was applied using diverse probe combinations specific for translocated chromosome segments. The average frequency of sperm nuclei bearing unbalanced products for t(7;10), t(15;17), t(6;13), and t(1;13) were 48.7%, 59.5%, 60.5%, and 62.9%, respectively. Frequencies of blastomeres comprising unbalanced products in cases with t(15;17), t(6;13), and t(1;13) were 80% (12 of 15), 60% (3 of 5), and 50% (2 of 4), respectively. Chi‐square test analysis showed significant differences in the meiotic segregation patterns due to the distribution and numbers of the chiasmatas that could depend on the size of the translocated segments (P < 0.001). In conclusion, FISH analysis of sperm and blastomere for reciprocal translocation carriers effectively estimates the approximate risk of unbalanced products and this result might ensure valuable genetic counseling.

Vitamin a deficiency in patients with common variable immunodeficiency.

Vitamin A, a naturally occuring antioxidant micronutrient, has immunomodulating effect in patients with immunodeficiency, including an influence on cytokine production and lymphocyte growth and functions. Vitamin A deficiency is associated with a shift from type 2 cytokines to predominantly type 1 cytokines. The aims of this study were to determine Vitamin A status in Common variable immunodeficiency (CVID) patients and the relationship between Vitamin A status and cytokines production. Serum Vitamin A, neopterin, TNF-alpha, IL-2, IL-4, and IL-10 levels were determined in 19 CVID patients and 15 healthy children. Effects of 9-cis retinal, Vitamin A derivative, on cytokines (TNF-alpha, IL-2, IL-4 and IL-10) production in lymphocytes were tested in vitro condition using lymphocyte cultures obtained from CVID patients and healthy children.Serum Vitamin A level in CVDI patients was, 21.1± 1.5 μg/dL, significantly (p < 0.001) lower than the value, 35.7± 1.8 μg/dL, observed in healthy children. Serum neopterin level in the patients was, 9.8± 2.9 nmol/L, higher (p < 0.05) than the value, 3.9± 0.7 nmol/L, observed in control group. Common variable immunodeficiency patients, serum IL-4 level was significantly (p < 0.05) lower than the value observed for healthy children. Serum TNF-alpha, IL-2 and IL-10 levels were similar in the patients and healthy children. Vitamin A derivative, 9-cis retinal, increased TNF-alpha and IL-4 production in cultured mononuclear cells obtained from control and CVID patients. Vitamin A derivative, also, increased IL-2 and Il-4 production in cultured mononuclear cells obtained from CVID patients.These results show that CVID patients have low serum Vitamin A levels and high serum neopterin levels. A supplementation with Vitamin A may have role in downregulation of inflammatory responses in CVID patients.

Reanalysis of human blastocysts with different molecular genetic screening platforms reveals significant discordance in ploidy status

ObjectiveThe objective of this study is to determine mosaicism and its effect on blastocysts; abnormal blastocysts determined by molecular testing were sequentially biopsied and retested.Material and methodWe re-biopsied 37 blastocyst-stage abnormal embryos from eight patients, which were reanalyzed to determine the level of concordance between biopsies and inter-laboratory congruence between reputable commercial PGS laboratories.ResultsThe main outcome measures were intra-embryo variation between sequential embryo biopsies and inter-laboratory variation between two PGS laboratories. The compatibility between both aCGH and NGS was found to be 11 % (3/27). Importantly, 9/27 (33 %) of embryos originally reported to be aneuploid, upon repeat assessment, were found to be euploid. The concurrence for SNP array and NGS was 50 % (3/6), and 17 % (1/6) of these abnormal embryos tested normal upon re-evaluation with NGS. NGS resulted 41 % (11/27) normal results when 27 of CGH abnormal embryos were retested. Concordance between aCGH and NGS was 4 % (1/27) whereas in three instances, gender discrepancy was observed with NGS when aCGH abnormal embryos were reanalyzed.ConclusionsThe results of these studies reinforce the prevalence of inconsistencies during PGS evaluation of trophectoderm biopsies possibly due to variations in platform sensitivity and heightening concerns over the clinical tractability of such technology in human ARTs..

Investigation of GSTP1 (Ile105V al) Gene Polymorphism in Chronic Myeloid Leukaemia Patients

Abstract The factors leading to the development of Chronic Myeloid Leukemia (CML) are not fully known. Associations between polymorphisms for genes encoding Glutathione S-transferase (GST) enzymes involved in Phase II detoxification reactions and susceptibility to some cancers have been shown in several studies. The aim of the present study was to investigate the influence of the GSTP1 (IIe105Val) gene polymorphism on human susceptibility to CML. Seventy-one CML patients and 67 control subjects with no cancer history were enrolled in our study. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify the GSTP1 (lle105Val) gene polymorphism. Genotypes were determined according to the bands that formed in agarose gels via gel electrophoresis. Leukocytes in the CML patient group were significantly different from those in the control group (p=0.0001). The frequency of the GSTP1 Val allele was found to be 22% in CML patients and 31% in controls. However, no statistical variation was found to exist between controls and patients in terms of the GSTP1 Val allele frequency (p=0.199). The relationship between the GSTP1 (IIe105Val) gene polymorphism and CML is not fully understood. Our results provide no evidence of a relationship between the GSTP1 (IIe105Val) gene polymorphism and susceptibility to CML in Turkish patients. However, these findings should be confirmed in studies with larger sample sizes.