Mehmet Elbistan

A Retrospective Study of Balanced Chromosomal Translocations in a Turkish Population

Abstract The balanced translocations are accepted as chromosomal rearrangements that do not generally reflect any phenotypic evidence. However, phenotypical influences can be seen in children of balanced translocation carriers due to the formation of partial monosomy and partial trisomy of any related chromosome. In this study, 25 cases that detected to have balanced translocation by cytogenetic analyses were evaluated with regard to their phenotypic features. Karyotype analyses of cases were taken out by using conventional peripheral blood culture method. It is estimated that 14 (56%) of these balanced translocation carriers had recurrent miscarriage, 5 (20%) had children with mental retardation, 3 (16%) had infertility, 2 (8%) had amenorrhea and 1 (4%) had mental retardation. When the cases were examined, it is understood that the increase in the frequency of miscarriage is the most frequent phenotypic feature in balanced translocation carriers as a result of the formation of unbalanced gametes.

Effects of subtelomeric copy number variations in miscarriages.

Abstract Purpose: This study was performed on miscarriage samples for chromosome analysis to detect copy number variations (CNVs) related to subtelomeric regions, and with these results we aimed to adapt multiplex ligation-dependent probe amplification (MLPA) method for prenatal diagnosis. Materials and methods: The cell cultures and DNA isolations were performed on 60 miscarriage samples. For maternal contamination analysis, DNA isolations and quantitative fluorescent polymerase chain reactions were done using peripheric blood of mothers who had miscarriages. We compared short tandem repeat peak profiles of miscarriage samples and mothers. The subtelomeric regions of the chromosomes were assessed using the MLPA method. Results: Of 43 miscarriage samples, 19 had normal karyotype (44.2%), 10 had numerical abnormalities (23.3%), and 2 had structural abnormalities (4.7%). Subtelomeric 16q duplication was determined in 2 of the 30 miscarriage samples investigated with MLPA method (6.6%). Conclusion: There is no statistically significant difference between two groups (p > 0.05). However, the fact that the 6.6% subtelomeric CNV found in miscarriage samples was not found in controls, showed that further studies are required. We recommend that the miscarriage samples of the couples with recurrent miscarriage should be analyzed in terms of subtelomeric CNV after the exclusion of other clinical reasons. Chinese abstract 目的：通过对流产物取样进行染色体分析来检测端粒近端区域基因拷贝数异变（CNVs）情况，旨在将多重连接探针扩增技术（MLPA）用于产前诊断。 材料与方法：对60例流产物样本进行细胞培养和DNA分离。采用母体外周血进行母体细胞污染分析、DNA分离及荧光定量聚合酶链反应。我们比较了流产样本和母血中短串联重复序列峰值情况。采用MLPA对染色体亚端粒区进行评估。 结果：43例流产样本中，19例核型正常（44.2%）。10例染色体数目异常（23.3%）2例结构异常（4.7%）。采用MLPA对30例流产样本进行检测，其中2例发生端粒区域16号染色体长臂复制（6.6%）。 结论：两组没有明显的统计学差异（p>0.05）。然而流产样本中发现6.6%端粒近端区域基因拷贝数异变，而控制组中没有发现，尚需进一步研究。我们建议对于存在复发性流产的夫妇在排除其他临床原因外应对流产物样本进行端粒近端区域基因拷贝数异变分析。

FMR1 gene mutation screening by TP-PCR in patients with premature ovarian failure and fragile-X

Abstract CGG repeat expansion in the FMR1 gene is associated with fragile X syndrome, fragile X-associated tremor/ ataxia syndrome and fragile X-associated primary ovarian insufficiency. In this study, FMR1 gene mutation screening was carried out in 50 patients. Among them, 12(%24) were POF and 19 (%38) were Fragile-X. We also examined the parents of the Fragile-X patients. DNA was extracted from blood with kit procedure. To examine expansion of the fragile-X CGG repeat, TP-PCR assay was performed and all amplicons were evaluated on an ABI3130XL Genetic Analyzer System by Fragman analysis. The data were analyzed by Gene Mapper Program. As a result of this study, the patients were identified with the fragile-X whose FMR1 gene CGG alleles have been observed in normal range. However, in patients who were referred with premature ovarian failure, pre-mutation frequency was observed as 6.6%. Only limited study in Turkish population reported frequency of pre-mutation carrier in POF and Fragile-X. Detection of pre-mutation carrier is important for next generation to have healthy siblings. We emphasize that TP-PCR technique is clear, reliable, sensitive, easy and fast method to detect pre-mutation. However, full mutations have to be examined by the technique of Southern blot in the diagnosis of fragile-X.

Evaluation of apoptotic cell death on liver and kidney tissues following administration of levetiracetam during prenatal period.

Abstract Objective: Levetiracetam is a new generation antiepileptic drug used in treatment of patients with epilepsy and has adverse effects on different tissues. We aimed to evaluate the apoptotic effects of levetiracetam exposure during pregnancy on liver and kidney tissues of rat pups. Methods: We analyzed the newborn rat pups exposed to levetiracetam during prenatal period. Fifteen pregnant female rats were divided into three groups. The group 1 and 2 rats were treated with different doses of levetiracetam (25 mg/kg/d and 50 mg/kg/d, respectively) from gestational days 1–22 during pregnancy. Group 3 (control group) was treated with the same volume of saline. Apoptosis was evaluated by the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) method. Liver and kidney tissues from rat pups were used for investigation. Results: The percent of TUNEL positive apoptotic cells in group 1 were 22 and 17.5 for kidney and liver, respectively. The percent of TUNEL positive apoptotic cells in group 2 were 20.9 and 20.9 for kidney and liver, respectively. The percent of TUNEL positive apoptotic cells in group 3 were 18.4 and 17.1, respectively, for kidney and liver. The apoptotic index was the same in kidney and liver tissues of all groups. Conclusion: Our results demonstrate that the prenatal exposure of levetiracetam has no apoptotic effects on liver and kidney of rat pups and, it has biosafety in pregnancy in terms of apoptosis. The first study evaluating the apoptotic effects on liver and kidney tissues following administration of levetiracetam during prenatal period.

A Case with Partial 9p Trisomy and Speech Impairment

DOI: 10.4328/JCAM.1226 Received: 20.07.2012 Accepted: 16.09.2012 Printed: 01.11.2015 J Clin Anal Med 2015;6(6): 796-8 Corresponding Author: Akın Tekcan, Ondokuz Mayis University, 55139 Kurupelit Samsun, Turkey. GSM: +905055719646 E-Mail: akintekcan@hotmail.com Özet Bu çalışmada, sitogenetik analiz amacıyla laboratuarımıza refere edilen 5 yaşında bir erkek çocukta saptanan der(15), ish t(9;15)(p12;p11,2) translokasyon ve olgunun fenotipik anomalileri arasındaki ilişkileri tartışmayı amaçladık. 5 yaşındaki erkek olgumuz konuşma bozukluğu ve gelişme geriliği şikayetlerine sahipken, olgunun aile bireylerinde herhangi bir fenotipik anomali bulunmamaktaydı. Olgunun aile öyküsünün değerlendirilmesinin ardından, periferik kan kültürü metodu kullanarak olgu ve aile bireylerinden elde edilen preparatlar GTG bantlama yöntemiyle değerlendirildi. Bunun yanında, olgunun annesi ve babasında yapılan sitogenetik analizler normal karyotiplere sahip olduklarını gösterdi. Olgumuzun sahip olduğu translokasyonun, bilinmeyen de novo mekanizmalar sonucu ortaya çıktığı kanaati edinildi. Bu çalışmada, olgunun fenotipik anomalileri ve genetik özellikleri arasındaki ilişkileri literatür ışığında tartıştık.

46, XY, t(5;8) (q33,2;q22,2) KARYOTİPLİ BİR FETÜS

OZET Bu calismada; ileri anne yasi nedeniyle prenatal tani amaciyla laboratuvara refere edilen bir kadin olgunun, de novo t(5;8)(q33,2;q22,2) dengeli resiprokal translokasyon tasiyicisi fetusunu tartistik. Olgunun aile oykusunun degerlendirilmesinin ardindan, periferik kan kulturu metodu kullanarak olgu ve aile bireylerinden elde edilen preparatlar GTG bantlama yontemiyle degerlendirildi. Ileri anne yasi nedeniyle prenatal tani amaciyla laboratuvara refere edilen kadin olgunun fetus’unden yapilan sitogenetik analizler sonucunda, fetus’un dengeli resiprokal translokasyon tasiyicisi oldugu goruldu. Fetus’un annesi, babasi ve iki kardesinde yapilan analizlerde; aile bireylerinin normal karyotiplere sahip olduklari goruldu. Saptanan dengeli resiprokal translokasyonun anne yasi ile iliskili olarak DNA tamir mekanizmalarinda olusan hata nedeniyle ortaya ciktigi kanaatine varildi. Bu calismada, fetus’un genetik ozelliklerini literatur isiginda tartistik. Anahtar kelimeler: Anne yasi, prenatal tani, kromozomal translokasyon

Dengeli resiprokal translokasyon taşıyıcısı bir olgu ve habitüel düşük

Bu calisma ile ailesinde dusuk oykusu bulunmayan, 6 kez dusuk yapip, sitogenetik analiz amaciyla laboratuvara basvuran bir kadin olguda saptanan de novo t(8;13)(p12;q14) dengeli resiprokal translokasyon ile habituel abortus arasindaki iliski degerlendirildi. Olgunun aile oykusunun alinmasinin ardindan, periferik kan kultur metodu ile olgu ve aile bireylerinden elde edilen preparatlar, Giemsa-Trypsin (GTG) bantlama metodu ile boyanarak degerlendirildi. Habituel abortus tanisi ile laboratuvara basvuran olgunun alti hamileligi de gelisim yetersizligi nedeniyle iki aylikken medikal mudahale ile sonlandirilmisti. Klinik incelemeler; olgunun fenotipik olarak normal oldugunu, sitogenetik incelemeler ise olgunun 46,XX, t(8;13)(p12;q14) resiprokal translokasyon tasiyicisi oldugunu gosterdi. Olgunun esi, annesi, babasi ve dort kardesinde yapilan sitogenetik analizlerden; tum bireylerin normal karyotipe sahip olduklari goruldu. Sonuc olarak, bu dengeli resiprokal trasnlokasyonun bilinmeyen de novo mekanizmalar sonucu ortaya ciktigi kanaatine varildi. Bu calismada, de novo dengeli bir resiprokal translokasyon tasiyan olgunun dusukleri ve olguda saptanan klinik bulgular arasindaki iliski tartisildi. A case with balanced reciprocal translocation carrier and habitual abortion In this study, we aimed to discuss the relation between habitual abortions and de novo balanced reciprocal translocation entity that determined from a woman case who applied to the laboratory with the aim of cytogenetic analysis by having 6 miscarriages and whose family has no miscarriage. Preparations obtained from the patient and her relatives by method of peripheric blood culture was banded by Trypsin Giemsa Banding (GTG) method after making her pedigree. A case with habitual abortions referred to our cytogenetic laboratory with six abortions. Her six pregnancy because of insufficiency development had been ended by medical application, when they had two months. Clinical examinations revealed that she has been normal phenotype, but conventional cytogenetic analyses showed that she had been a carrier of de novo balanced reciprocal translocation (46,XX, t(8;13)(p12;q14)). On the other hand, cytogenetic analyses of her husband, father, mother and four siblings revealed that they had been normal karyotypes. In results, it was convinced that the balanced reciprocal translocation may be the result of unknown de novo mechanism that without phenotype feature. We discussed relation between clinical findings and abortions of case who carrier of a de novo balanced reciprocal translocation. J. Exp. Clin. Med., 2012; 29:312-314