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Arguden, Yelda Tarkan/0000-0002-5405-3365; Ozbek, Ugur/0000-0001-5319-0547; Akcakaya, Nihan Hande/0000-0001-8414-4017 Beta-propeller protein-associated neurodegeneration (BPAN) is an X-linked rare dominant disorder of autophagy. The role of WDR45 has been implicated in BPAN almost exclusively in females possibly due to male lethality. Characterization of distinctive clinical manifestations and potentially the complex genetic determinants in rare male patients remain crucial for deciphering BPAN and other X-linked dominant diseases. We performed whole exome sequencing (WES) followed by segregation analysis and identified a novel nonsense and mosaic variant in WDR45, namely NM_007075.3:c.873C>G; p.(Tyr291*) in an affected male at the age of 34. His biphasic medical history was compatible with BPAN, which was characterized by delayed psychomotor development, intellectual disability, and progression into dystonia parkinsonism in his twenties. The variant had an apparently mosaic pattern both in whole exome and Sanger sequencing findings. In order to figure out if mosaicism was restricted to this variant or related to a chromosomal level mosaicism, we used our in-house WES data from 129 unrelated individuals to calculate the threshold values of male and female X chromosome heterozygosity (XcHet) in WES data for our pipeline. A background level of heterozygous variants on X chromosome excluding the pseudoautosomal loci is an observed phenomenon in WES analysis and this level has been used as a quality measure. Herein, we suggest utilization of this measure for detection of digital anomalies of the X chromosome in males by potentially observing a higher XcHet value than the threshold value. This approach has revealed a variant level mosaicism in the affected male, which was further supported with cytogenetic analyses. Scientific Research Projects Coordination Unit of Istanbul UniversityIstanbul University [TDK-2017-26646] This study was funded by the Scientific Research Projects Coordination Unit of Istanbul University, Project Number TDK-2017-26646. WOS: 000458670800006 30612247 Q3

Edinsel faktör inhibitörleri çoğunlukla kan pıh- tılaşma proteinlerini direk olarak engelleyen antikorlardır. Bu antikorlar; hemofili A’daki an- tikor gelişimi, post partum dönem, çeşitli im- münolojik hastalıklarla ilişkili olan durumlar, çeşitli kanserlerle ilişkili olan durumlar ve yaşlı hastalar gibi birçok klinik durumda görülür. Önemli oranda mortalite ve morbiditeye neden olan edinsel hemofili A (AHA); öz geçmiş ve soy geçmişinde kanama hastalığı olmayan, kanama ve uzamış aPTT’si olan hastalarda ayırıcı tanıda düşünülmelidir. Edinsel hemofilinin tedavi stra- tejisi hakkında henüz bir görüş birliği yoktur. Biz burada; immünsupressif tedavi ile başarılı bir şekilde tedavi edilen post partum edinsel (AHA)’lı bir vaka bildirdik. Acquired factor inhibitors are antibodies that inhibit directly blood clotting proteins. These are seen in many clinical situations such as inhi- bitors in hemophilia A, postpartum, in older pa- tients, in association with various immunologic disorders and various malignancies. Acquired hemophilia A which can cause a considerable proportion of mortality and morbidity, should be taken in consideration as a differentional di- agnosis in patients who have prolonged aPTT and bleeding without a personal or family his- tory of bleeding disorder. There is no consensus about the treatment strategy of acquired he- mophilia A yet. We reported a case of postpar- tum acquired hemophilia A who was treated with immunosupressive therapy.

Drug induced autoimmune hemolytic anemia is a well-known complication of drug therapy but it is often misdiagnosed. Drug induced autoimmune hemolytic anemia is difficult to differantiate from classical autoimmune hemolytic anemia. Here, we have reported a case with autoimmune hemolytic anemia might be caused by drugs such as teicoplanin, imipenem and amphotericin B. In our case, on the fifteenth postadmission day was occur autoimmune hemolytic anemia. At this while, chemotherapy of patient had been completed and the patient have been taking antibiotherapy which include teicoplanin, imipenem and amphotericin B. Antibiotherapy could not be stopped because of febrile neutropenia. Symptoms and sings of anemia improved with prednisolon therapy. Suspicious drug must be stopped in drug induced autoimmune hemolytic anemia but in the conditions that drug could not be stopped, steroid treatment can be used in the treatment of hemolytic anemia.ilaca bağlı otoimmün hemolitik anemi, ilaç tedavisinin iyi bilinen bir komplikasyonudur fakat sıklıkla yanlış tanı konulur. ilaca bağlı otoimmün hemolitik anemiyi klasik otoimmün hemolitik anemiden ayırmak zordur. Biz, burada; teikoplanin, imipenem, amfoterisin B gibi ilaçların neden olabildiği otoimmün hemolitik anemili bir olgu sunmaktayız. Olgumuzda; kabul sonrası 15. günde otoimmün hemolitik anemi gelişti. Bu sırada hastanın kemoterapisi tamamlanmıştı ve hasta teikoplanini imipenem ve amfoterisin B`yi içeren antibiyotik tedavisi almaktaydı. Febril nötropeni nedeni ile antibiyotik tedavisi kesilemedi. Aneminin semptom ve bulguları prednizolon tedavisi ile düzeldi. ilaca bağlı otoimmün hemolitik anemide, şüpheli ilaç kesilmelidir fakat ilacın kesilemediği durumlarda steroid tedavisi hemolitik aneminin tedavisinde kullanılabilir.

Chronic eosinophilic leukaemia is a rare myeloproliferative disease different from the chronic myeloid leukaemia. It is a haematologic malignancy that must be considered separately from other causes of eosinophilia due to its remarkable clonal eosinophilia. Here, we describe a case with chronic eosinophilic leukaemia which was initially hypereosinophilic (eosinophil count: 85.4 x 109/L) and displayed blastic transformation after a 9 months follow up. We suggest the invasion of spleen, probable invasion of the liver and the blastic transformation of this case must be discerned as a different entity rather than the other causes of eosinophilia.Kronik eozinofilik lösemi (CEL) nadir görülen ve kronik miyeloid lösemiden farklı miyeloproliferatif bir hastalıktır. Klonal eozinofil artışı nedeniyle diğer eozinofili nedenlerinden ayrı ele alınması gereken hematolojik bir malignitedir. Burada hipereozinofili ile seyreden (eozinofil sayısı: 85.4x109/L) ve takibe alındıktan dokuz ay sonra blastik transformasyon gösteren bir kronik eozinofilik lösemi olgusu sunmaktayız. Bu tablonun dalak tutulumu, muhtemel karaciğer tutulumu ve blastik transformasyonla sonlanması nedeni ile diğer eozinofili nedenlerinden ayırdedilmesi gerektiğini düşünüyoruz.

Lymphoma is the second most common neoplasm of the head and neck after squamous carcinoma. The majority of lym¬phomas involving the head and neck are non-hodgkin's lymphomas. Hodgkin's lymphoma is rare in Waldeyer's ring. Between 1999 and 2006, the medical records and pathology data of all newly diagnosed, previously untreated adult patients with Waldeyer's ring lymphomas were retrospectively reviewed. Pathologic specimens were adopted according to WHO his¬tologic classification. All patients were clinically staged with history and physical examination, routine hematologic and bio¬chemical profiles, chest X-ray, and computerized tomography of the head and neck, chest, abdomen and pelvis. All patients were treated with chemotherapy. Approximately one month after the end of the scheduled initial management, patients were restaged for evidence of residual disease with physical examination, laboratory profiles and relevant radiologic studies. Total patient number was 11 in our institution. Complete remission was achieved in 6 patients and partial remission in 3 patients; 1 patient did not achieve remission and 1 patient with anaplastic large cell lymphoma died. Patients who are alive are still being followed in our institution. The progression of patients with lymphoma is closely associated with the diagnosis, stage and histologic grade of the disease. This series characterized the clinicopathologic features and outcomes of adult patients. Our data have shown that there is relatively good survival in these diseases but more patients must be evaluated for mean¬ingful results.Lenfoma, yassı hücreli karsinomadan sonra boyun bölgesinin en sık görülen ikinci tümörleridir. Baş ve boyun bölgesini tutan lenfomaların çoğu non – hodgkin lenfomalardır. Hodgkin lenfomalar Waldeyer halkasında nadirdir. 1999 ve 2006 tar¬ihleri arasındaki tıbbi ve patolojik kayıtlarımızdan daha önce tedavi almamış, yeni tanılı Waldeyer halkası lenfomalı erişkin hastaların bilgilerini geriye yönelik olarak gözden geçirdik. Patolojik örnekler Dünya Sağlık Örgütü (WHO ) histolojik sınıflandırmasına göre uyarlandı. Tüm hastalar hikaye ve fizik muayene, rutin hematolojik ve biyokimyasal tetkikler, göğüs röntgeni, baş – boyun, göğüs, karın ve pelvik tomografilerle evrelendirildi. Hastalar tedavi şemasının bitiminden yaklaşık bir ay sonra hastalık kalıntıları açısından tekrar evrelendirildi. Bölümümüze kayıtlı toplam 11 hasta vardı. Altı hastada tam yanıta, üç hastada kısmi yanıta ulaşıldı. Bir hastada yanıt sağlanamadı. Anaplastik büyük hücreli lenfoması olan bir hasta tedavisi sürerken kaybedildi. On hastamız halen polikliniğimizin takibindedir. Lenfoma hastalarının seyirleri hastalığın evresi ve histolojik türü ile yakın ilişkilidir. Burada erişkin hastalarımızın klinikopatolojik özellikleri ve sonuçları özetlenmiştir. Bu hastalıktaki verilerimiz sağkalımın nispeten iyi olduğunu göstermektedir. Sonuçların anlamlı olabilmesi için daha fazla has¬tanın değerlendirilmesi gereklidir.

The Philadelphia (Ph) chromosome, consisting of the t(9;22)(q34;q11) translocation, is observed in ~90% of patients with chronic myeloid leukemia (CML). Variant Ph translocations are observed in 5%-10% of CML patients. In variant translocations 3 and possibly more chromosomes are involved. Herein we report 6 CML patients with variant Ph translocations.Bone marrow samples were examined using conventional cytogenetic meth ods. Fluorescence in situ hybridization (FISH) with whole-chromosome paints and BCR-ABL 1D probes were used to confirm and/or complement the findings, and identify rearrangements beyond the resolution of conventional cytogenetic methods.Variant Ph translocations in the 6 patients were as follows: t(7;22)(p22;q11), t(9;22;15)(q34;q11;q22), t(15;22)(p11;q11), t(1;9;22;3)(q24;q34;q11;q21), t(12;22)(p13;q11), and t(4;8;9;22)(q11;q13;q34;q11).Among the patients, 3 had simple and 3 had complex variant Ph translocations. Two of the presented cases had variant Ph chromosomes not previously described, 1 of which had a new complex Ph translocation involving chromosomes 1, 3, 9, 22, and t(1;9;22;3)(q24;q34;q11;q21) apart from a clone with a classical Ph, and the other case had variant Ph translocation with chromosomes 4, 8, 9, and 22, and t(4;8;9;22)(q11;q13;q34;q11) full complex translocation. Number of studies reported that some patients with variant Ph translocation were poor responders to imatinib. All of our patients with variant Ph translocations had suboptimal responses to imatinib, denoting a poor prognosis also. Variant Ph translocations may be important as they are associated with prognosis and therapy for CML patients.AMAÇ: t(9;22)(q34;q11) sonucu oluşan Philadelphia (Ph) kromozomu, kronik miyeloid lösemi (KML) olgularının %90’ dan fazlasında gözlenir. KML hastalarının %5-10 unda varyant Ph translokasyonları bulunur. Varyant translokasyonlar üç ve daha fazla kromozom içerebilmektedir. Bu çalışmada varyant Ph translokasyonlu 6 KML olgusu sunulmaktadır. YÖNTEMLER: Kemik iliği örnekleri konvansiyonel sitogenetik kullanılarak incelendi; BCR-ABL 1D problarının kullanıldığı Floresan İn Situ Hibridizasyon (FISH) yöntemi bulguların doğrulanması ve konvansiyonel sitogenetik yöntemlerinin tespit etmekte yetersiz kaldığı yeniden düzenlemelerin tanımlanması amacıyla uygulandı.Çalışmada yer alan 6 hastanın varyant Ph translokasyonları: t(7;22)(p22;q11), t(9;22;15)(q34;q11;q22), t(15;22)(p11;q11), t(1;9;22;3)(q24;q34;q11;q21), t(12;22)(p13;q11) ve t(4;8;9;22)(q11;q13;q34;q11) dır. SONUÇ: Üç olguda basit, 3 olguda ise karmaşık (kompleks) varyant Ph translokasyonları saptamış bulunuyoruz. Olgularımızın ikisi daha önce bildirilmeyen varyant Ph kromozomları taşıyorlardı. Bu olgulardan biri klasik Ph’lı bir klonun yanısıra 1, 9, 22 ve 3 numaralı kromozomları içeren t(1;9;22;3)(q24;q34;q11;q21) formüllü yeni bir kompleks Ph translokasyonuna; diğeri ise 4, 8, 9 ve 22 numaralı kromozomları içeren t(4;8;9;22)(q11;q13;q34;q11) kompleks translokasyonlu varyant Ph’ya sahiptiler. Varyant Ph’lı 6 olgunun tümü kötü prognoza işaret eden yetersiz imatinib cevabı gösterdiler.

Chronic myeloid leukaemia (CML) is a clonal haematological disease characterised by t(9;22)(q34;q11) which is called Philadelphia (Ph) chromosome. Highly improved haematological and cytogenetic results were obtained in chronic phase CML with the introduction of imatinib. Occurrence of additional cytogenetic abnormalities in Ph(+) cells is defined as clonal evolution (CE) and considered to be a preceding sign for acceleration. The most common additional chromosomal changes are +8, +Ph, i(17q), +19, -Y, +21, +17 and-7. The aims of this study were to delineate the occurrence pattern of cytogenetic clonal evolution in our cohort of CML patients and to investigate the impact on the course and prognosis of CML. Additional clonal chromosomal changes in Ph(+) cells were observed in 20 cases (19%). The abnormalities seen were monosomy 21 (%35), -17 (%30), -19 and +8 in (%25), -7, -8, -13, -15, -22, +Ph, and different marker chromosomes (%20), -Y, -12, -14, -16, -20 (%15), +Y, -10, -18 (%10), and -X, -3, -9...

Cytogenetic analysis of a girl with moderate mental retardation and dysmorphic features revealed a 46,XX/47,XX,+mar karyotype. Fluorescence in situ hybridization using chromosome specific alpha satellite probes showed that the supernumerary marker originated from the X chromosome. To our knowledge, this is the first reported case of a female patient mosaic for a supernumerary small marker chromosome derived from X, and hence mosaic for trisomy of the pericentric region of the X chromosome.

HER-2 amplification is a biomarker for identifying patients who respond to trastuzumab and has been evaluated as a factor predicting the response to anthracyclines. The relationship between HER-2 and response to anthracycline therapy may also be the result of the close localization of TOP2A on 17q. It has been a matter of debate whether these two genes, HER-2 and TOP2A, behave separately on different amplicons or act together thus making it possible to predict the TOP2A status from the HER-2 status. In this study TOP2A, HER-2 and chromosome 17 aneusomy were investigated by fluorescent in situ hybridization (FISH) in 50 consecutive breast cancer patients. HER-2 amplification was detected in 11 patients (22%) and TOP2A changes were seen in 6 patients (12%); two amplifications and two deletions were observed in HER-2-amplified cases and two deletions in HER-2-nonamplified cases. Three of the TOP2A-deleted cases had polysomy 17. HER-2 copy number was higher than the TOP2A copy number in one patient with co-amplification. Polysomy was observed in 9 cases (18%) and monosomy in 6 cases (12%). Aneusomy was the sole anomaly in 11 patients (22%). We conclude that the TOP2A status cannot be predicted from the HER-2 status and evaluation of the TOP2A status only in patients with HER-2 overexpression may lead to missing cases with TOP2A deletion with possible resistance to therapy. Other factors modulating topo IIα activity may also affect the response to therapy. Studies evaluating different parameters that can modulate topo IIα activity and the response to the drugs targeting the enzyme are necessary.

Amac: Bu calismada akut lenfoblastik losemili (ALL) hastalarda MYC gen bolgesindeki yeniden duzenlenmelerin konvansiyonel sitogenetik ve interfaz FISH yontemleriyle incelenmesi amaclanmistir. Yontemler: Calisma, ALL tanisiyla laboratuvarimiza gonderilen 25 olgudan alinan kemik iligi orneginde gerceklestirildi. On dort cocukluk cagi ve 11 yetiskin ALL hastasi incelendi. Konvansiyonel sitogenetik inceleme icin G bantlama yontemi, Floresan in situ hibridizasyon (FISH) yontemi icin MYC breakapart probu (Cytocell) kullanildi. Bulgular: Toplam 25 olgunun 2’sinde (%8) degerlendirilebilecek metafaz elde edilemedi. Kromozom analizi ger- ceklestirilen 23 olgunun 9’unda (%39,1) normal karyotip saptanirken, 6 olguda kromozom sayi anomalileri, 4 olguda yapi ve 4 olguda ise hem sayi hem de yapi anomalileri gozlendi. MYC gen bolgesini icine alan tek sitogenetik anomali olarak bir olguda (%4) t(8;14)(q24;q32) saptandi. Olgularin tumunde FISH analizinden sonuc alindi ve 3 olguda (%12) MYC bolgesinde FISH yontemi ile yeniden duzenlenme oldugu gosterildi. Sonuc: Iki yontem karsilastirildiginda MYC gen bolgesinin yeniden duzenlenmelerinin gosterilmesinde FISH yonteminin daha duyarli oldugu, ancak konvansiyonel sitogenetik yontemlerin de kromozomlarda meydana gelen tum degisimlerin ortaya konmasinda etkili oldugu gozlendi. Bu nedenle tek bir anomali arastirilan durumlarda dahi iki yontemin birlikte kullaniminin daha etkili olacagi sonucuna varildi. Anahtar kelimeler: Akut lenfoblastik losemi, MYC, sitogenetik, floresan in situ hibridizasyon

The expression of common fragile sites (c‐fra) and frequency of chromosomal aberrations were studied in peripheral lymphocytes of 50 healthy Turkish individuals (26 males and 24 females from 1 to 87 years of age) after induction with aphidicolin (APC), 5′‐fluorodeoxyuridine (FUdR), and caffeine. A correlation was seen between age and the frequency of chromosomal aberrations in APC and caffeine treated cultures, but there were no significant differences in the frequencies of chromosomal aberrations between males and females in any of the treatments. The mean frequency of aberrations induced by FUdR was significantly higher than that induced by APC and caffeine. A chromosome aberration is defined as a fragile site when present in 1% of the cells analyzed from each culture and in at least 50% of the individuals studied. Using these criteria, 12 c‐fra were observed in the three treatments: 1p21, 1q21, 2p11‐q11, 3p14, 4q31, 6q26, 7q22, 7q32, 8q24, 11q23, 16q23, and Xp22. Sites 3p14, 16q23, and Xp22 were the most frequently observed c‐fra, with only the frequency of Xp22 being significantly increased in females in APC treated cultures. The results of these studies are important as a base against which the effects of other clastogenic and environmental agents, as well as genetic background, can be compared.

We report on 2 Turkish families with children who had bilateral anophthalmia, upper and lower limb abnormalities, mental retardation and consanguineous parents. We have evaluated the 2 cases in the first family and the only case in the second as anophthalmia-Waardenburg syndrome. This is an extremely rare autosomal recessive syndrome.

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Objective: Vascular events are a common complication in patients with polycythemia vera (PV) and essential thrombocythemia (ET). This study aimed to analyze the association between PAI-1 4G/5G and ACE I/D gene polymorphisms, and leukocytosis with thrombosis in patients with PV and ET. Material and Methods: In total, 64 patients with ET and PV were evaluated. Arterial or venous thrombosis, such as cerebral transient ischemic attack, ischemic stroke, myocardial infarction, peripheral arterial thrombosis, deep venous thrombosis, and pulmonary embolism, were defined as a vascular event. DNA samples were screened for mutations via reverse hybridization strip assay. Results: In terms of PAI-1 gene polymorphism, the frequency of the 4G and 5G allele was 48.5% and 51.5%, respectively. The ACE allele frequency was 51.2% and 48.8% for D and I, respectively. There wasn’t an association between occurrence of vascular events and the frequency of any allele. In terms of occurrence of vascular events, there weren’t any significance differences between the patients that were carrying the ACE D/D homozygous allele to ACE I/D and those that carried the I/I allele (P = 0.93). There wasn’t a significant difference in occurrence of vascular events between the PAI-1 5G/5G homozygote allele carriers, and the 4G/5G and 4G/4G allele carriers (P = 0.97). Vascular events were significantly more common in the patients with leukocytosis (leukocyte count >10 × 109 L–1) than in those without leukocytosis (leukocyte count ≤10 × 109 L–1) (P = 0.00). Age >60 years was also a significant risk factor for occurrence of vascular events(P = 0.008). Conclusion: PAI-1 and ACE gene polymorphisms were not considered new risk factors for thrombosis in PV and ET patients. On the other hand, leukocytosis at diagnosis was associated with the occurrence of vascular events in the patients with ET and PV.

3p abnormalities are the most frequent chromosome abnormalities in small cell lung cancer (SCLC). To date these abnormalities have only been observed in cells derived from tumor tissues. It is thought that cancer-related chromosome abnormalities in peripheral lymphocytes could help to predict cancer development, prognosis, and future metastasis. We report clonal and nonclonal 3p abnormalities in the peripheral lymphocytes of two patients with SCLC. A standard T-lymphocyte culture method and GTL banding technique were applied to the samples, and various clonal and nonclonal chromosome 3 abnormalities, i.e., −3, del(3)(p24), del(3)(p21), del(3)(p11), del(3)(q22), inv(3)(p14q29), and inv(3)(q21q29) were observed. Efforts have been made to understand if there are cancer-related chromosome abnormalities in lymphocytes and the suitability of these abnormalities to predict cancer development or metastases. As far as we know, this is the first report on chromosome 3 abnormalities in lymphocytes. Since 3p abnormalities are specific for SCLC, it is important to show that these cancer-related abnormalities can be found in blood cells.

Nötropenik enterokolit, çıkan kolon ve çekumun nekroz ve perforasyonu ile karakterize akut bir tablodur. Sıklıkla lösemi ile ilişkili olmakla birlikte solid tümörlü hastalarda, multipl miyelomda, aplastik anemi, AIDS ve siklik nötropenide de görülür. Yirmi beş yaşına erkek hasta akut miyelositer lösemi tanısı ile yatırıldı. İdarubisin ve sitozin arabinozid tedavisi başlanan hastada yüksek ateş, karında hassasiyet ve şiddetli ağrı, kanlı ishal gelişti. Direkt batın grafisinde hava sıvı seviyeleri saptanan ve acil olarak ameliyat edilen hastaya tiflitis tanısı kondu, nekroze ince bağırsak bölümü rezeke edildi. On dokuzuncu günde yeniden şiddetli abdominal ağrı, hassasiyet, kanlı ishal ve trombositopeni gelişen hasta yeniden ameliyata alındı. İkinci kez ameliyata alınan hastaya ileyal rezeksiyon yapılarak kolostomi açıldı. Ameliyat sonrası günlerde trombositopeni, kanama pıhtılaşma zamanında bozulma ve gastrointestinal sistem kanaması görülen hasta, tüm tedavilere karşın taşikardi, takipne, bilinç değişikliği ve sepsis kliniği ile kaybedildi. Neutropenic enterocolitis is an acute syndrome characterized by cecal and ascending colon inflammation that may progress to necrosis and perforation. It is most often associated with leukemia but has also been described in patients with solid tumors, multiple myeloma, aplastic anemia, AIDS, and cyclic neutropenia. Twenty-five year old male patient was admitted with a diagnosis of acute myeloid leukemia. Severe fever, abdominal sensitivity and severe pain and diarrhea with blood developed in the patient treated idarubicin and cytosine arabinoside. Direct abdominal radiogram revealed air-fluid levels, the patient was diagnosed as typhlitis and taken to an emergency operation in which the necrotised small bowel was resected. Severe abdominal pain and sensitivity, diarrhea with blood and thrombocytopenia developed again on the 19th day on which the patient was reoperated. Ileal resection and colostomia was performed on this second operation. Thrombocytopenia, prolonged bleeding and coagulation times and gastrointestinal bleeding was observed. Despite all treatment efforts, the patient developed tachycardia, tachipnea, cognitive changes and sepsis and died.

Sister chromatid exchange (SCE) and chromosome aberrations (CA) in peripheral lymphocytes has been widely used in assessing exposure to mutagens and carcinogens. One of the extensively studied genotoxins is benzo[alpha]pyrene (BaP). We studied the ability of BaP to induce SCE and CA in 16 glutathione S-transferase M1 (GSTM1)-positive and 15 GSTM1-null individuals by analyzing 72-h whole-blood lymphocyte cultures, either BaP-untreated (controls) or treated with 5 µM of BaP for 24 or 48 h. There was no differences in the level of BaP-induced chromosomal aberrations between GSTM1-positive or null individuals when the cells were BaP-exposed for 24 h (0.083 ± 0.059 vs. 0.090 ± 0.058) or 48 h (0.092 ± 0.057 vs. 0.096 ± 0.050. The frequency of SCE in controls was GSTM1-positive = 2.96 ± 0.35 and GSTM1-null = 3.23 ± 0.56 while that for BaP-treated lymphocytes was GSTM1-positive = 5.56 ± 0.83 and GSTM1-null = 6.09 ± 1.11 and were not statistically significant. The rates of BaP-induced in vitro chromatid and chromosome-type gaps and breaks were similar in all groups, although GSTM1-null genotype chromatid-type breaks were more frequent (0.064 ± 0.039 per metaphase) than chromosome-type breaks (0.032 ± 0.027 per metaphase) after 48 h treatment with BaP (p < 0.001). These findings suggest that BaP-induced in vitro SCE and CA are not influenced by the GSTM1 genotype.

Background: A large number of studies have demonstrated that various kinds of DNA damage accumulate during aging and that oxidative stress possibly contributes to this process. Glutathione S-transferase M1 (GSTM1) can prevent their possible effects on DNA via detoxification of reactive substances that induced oxidative stress. Objective: To investigate the relationship between GSTM1 polymorphism and DNA sensitivity to oxidative stress with age, we used micronucleus (MN) frequency as a marker of DNA damage in lymphocytes from young and elderly subjects. Methods: This study was performed in 30 young (age range 20–36 years) and 30 elderly (age range 66–87 years) healthy individuals who were chosen on the basis of their GSTM1 genotype (15 GSTM1 null and 15 GSTM1 positive for each group). Lymphocytes were cultured after Ficoll isolation and treated for 48 h with a 30-µM dose of cumene hydroperoxide (CumOOH), a dose that does not decrease cell viability. Results: There was no significant difference in the MN frequency observed in control cultures from young and elderly individuals. However, the MN frequency in CumOOH-treated cultures was significantly higher in the elderly group than the young group (p < 0.001). No association was found between the GSTM1 phenotype and CumOOH-induced MN frequency. Conclusions: The results suggest that lymphocytes of elderly individuals are more susceptible to in vitro MN induction by CumOOH. However, this difference in susceptibility is not explained by the lack of GSTM1.

A 39 year old male with primary infertility was diagnosed as having Klinefelter syndrome by conventional cytogenetic analysis, which also showed an abnormal chromosome 12. Fluorescence in situ hybridisation (FISH) analysis of the aberrant chromosome using a 12 specific centromeric probe showed a break in the alphoid repeats followed by an inversion within the short arm, resulting in a pseudodicentric chromosome. Further FISH analyses using telomeric and subtelomeric probes showed that the other breakpoint was in the subtelomeric region of the short arm. The karyotype is designated 47,XXY,inv(12)(p10p13.3). To our knowledge this is the first report of a case of "centric inversion".