Vincristine is a widely used chemotherapeutic agent in the treatment of childhood malignancies. Neuropathy is the most common adverse effect. CYP3A4 and CYP3A5 enzymes of cytochrome p450 enzyme system are responsible in vincristine metabolism. Genetic polymorphism may alter the vincristine metabolism and the neurotoxicity rate. In this study, distribution of CYP3A5 alleles among Turkish children with malignancies, relation between CYP3A5 genotype and neurotoxicity rates, as well as severity and duration of neuropathy and total vincristine doses were investigated. Patient group consisted of 115 patients (age, 1 to 17 y) with acute lymphoblastic leukemia and solid tumors, who were treated with vincristine consisting chemotherapy protocols. Control group consisted of 50 children without any neurological symptom or disorders. All patient files were reviewed for presence and severeness of neurotoxicity symptoms. Blood samples were obtained and CYP3A5 genotypes were analyzed. Neurotoxicity occurred in 20.8% of patients. Although it was found to occur more frequently after 4 doses of vincristine, and rates were higher in the low-dose vincristine group suggesting other contributing factors. Although neurotoxicity rate in the CYP3A5*1/*3 genotype was 17.6%, it was 21.6% in the CYP3A5*3/*3 genotype and the difference was not statistically significant (P<0.05). This study suggested that vincristine-related neurotoxicity is dose-independent and genotype is not the only causative factor in the occurrence of neurotoxicity in these patients.

Although the patients who underwent CTA were exposed to a greater amount of radiation, the radiation-induced genetic damage was similar with both types of the procedures.

Objective. The association of DRD2 rs1800497 (TaqIA) polymorphisms and schizophrenia has been studied in a number of populations, but the results are contradictory. We aimed to define Taq IA allelic differences between schizophrenic and healthy subjects. Methods. The schizophrenic group consisted of 99 schizophrenic inpatients, diagnosed and treated at Gazi University Hospital Psychiatry Service, the healthy group was composed of 109 subjects who did not suffer from any psychiatric or organic diseases. High molecular weight genomic DNAs were prepared from peripheral venous blood cells by using proteinase K digestion followed by salt extraction method. Target DNA amplification of DRD2 gene (Taq1A, 310-bp region) was performed by polymerase chain reaction (PCR) with the primers 5014 and 971. Results. Of the 208 subjects involved in the study, 98.6% had A1 allele (hetero- or homo-zygote) and 1.4% had A2 allele (homozygote). While all schizophrenia patients had A1 allele, 97.2%, of the healthy subjects (n=106) had A1 allele and there was no significant difference between the groups. Conclusion. This study was the first study related to DRD2 polymorphism conducted in a Turkish schizophrenic patient sample. A great percentage of our sample has A1 allele. Our study could not find a significant association between schizophrenia and DRD2 rs1800497 polymorphism.

Makale bilim dalı: Tıbbi Genetik Makale başlığı: İnfertil erkek hastalarda karyotip analizi ve Y kromozom mikrodelesyon analiz sonuçları. Kısa başlık: İnfertil erkeklerde genetik anomaliler. Öz Amaç: İnfertilite çiftlerin %15'inde görülen bir problemdir. Oligozoospermi ve azoospermi kaynaklı erkek infertilitesi tanısı alanların %30'unun etiyolojisinde genetik nedenler sorumludur. Bu retrospektif çalışmada, merkezimize başvuran infertil erkeklerde yardımcı üreme teknikleri uygulanmadan önce hem kromozomal yapının belirlenmesi hem de Y kromozomu üzerindeki azoospermik faktör (AZF) bölgesinin mikrodelesyonunun belirlenmesi amaçlanmıştır. Gereç ve yöntem: Laboratuvarımıza rutin analizler için başvuran 675 hasta çalışıldı. Bu hastalardan konvansiyonel sitogenetik yöntemle periferik kandan kromozom analizi yapıldı ve Y kromozom mikrodelesyon belirleme kiti kullanılarak fragman analizi yöntemi ile Y kromozomu mikrodelesyonu araştırıldı. Bulgular: 675 hastanın 75'inde sitogenetik ve 21'inde moleküler, 2'sinde hem sitogenetik hem moleküler düzeyde anomali belirlendi. Anomalili karyotipe sahip hastalarda sayısal ve yapısal (resiprokal ve robertsonian tip translokasyon, inversiyon, ring kromozom gibi) anomaliler saptandı. Y mikrodelesyon belirlenen hastaların 2'sinde AZFa, 1 hastada AZFb, 13 hastada AZFc/d (c+ proksimal c), 6 hastada AZFb/c/d, 1 hastada AZFc/d ve kısmi AZFa bölgelerinde mikrodelesyon saptandı. Sonuç: Çalışmamız kromozom anomalilerinin ve Y kromozomu mikrodelesyonunun erkek infertilitesinin önemli bir nedeni olduğunu ve bu nedenle infertil hastalarda, kromozom analizi ve Y kromozomu mikrodelesyon testlerinin yapılmasının, erkek kaynaklı infertilitenin açıklanmasında gerekliliğini göstermektedir. Anahtar kelimeler: Erkek infertilitesi, kromozomal anomali, Y kromozom mikrodelesyonu. Title: Karyotype analysis and Y chromosome microdeletion analysis results in infertile male patients.

Van den Ende–Gupta syndrome (VDEGS) (MIM#600920) is characterized by skeletal and craniofacial abnormalities that include prominent ears, downslanting palpebral fissures, blepharophimosis, hypoplastic maxilla with or without a cleft palate, a narrow and convex nasal bridge and an everted lower lip, camptodactyly and arachnodactyly. Intelligence is normal. Recent studies have reported that patients with VDEGS have pathogenic variants in the SCARF2 gene on chromosome 22q11.21. Here, we report two Turkish patients with two novel variants [c.2291_2292insC (p.Ser765LeufsTer6) and c.488G>A (p.Cys63Tyr)] in the SCARF2 gene. In silico analysis predicted that both of these novel variants were pathogenic. To the best of our knowledge, this is the first case report of this syndrome in Turkey.