Двунитевые разрывы ДНК спермиев у пациентов с нормозооспермией и патозооспермией

The levels of double-strand DNA breaks as a severe disruption of genome integrity were studied using the neutral version of the comet assay in the sperm samples of the men of the Belarusian population with normozoospermia and pathozoospermia, including asthenozoospermia, oligozoospermia, oligoasthenozoospermia, and other combined forms of pathozoospermia. It was demonstrated that double-strand DNA breaks have a large proportion (about 44–50 % on average) of the total number of DNA damage (singleand double-strand breaks, alkaline-labile sites, etc.) analyzed with the alkaline version of the comet assay recommended by the World Health Organization. Higher levels of sperm double-strand DNA breaks were established in the pathozoospermia group and in asthenozoospermia subgroup compared to the normozoospermia group. It was also shown that the levels of double-strand breaks observed at pathozoospermia correspond to the mutagenic effect in vitro of high concentrations (10–30 μg/ml) of bleomycin sulfate that acts as a strong radiomimetic, which points to a significant disruption of the DNA integrity at pathozoospermia. In general, the data obtained demonstrate the usefulness of the sperm double-strand DNA break analysis for male infertility diagnostics.С использованием нейтральной версии метода ДНК-комет изучены уровни двунитевых разрывов ДНК − грубых нарушений целостности генома – в образцах спермы мужчин из белорусской популяции при нормозооспермии и патозооспермии, включая астенозооспермию, олигозооспермию, олигоастенозооспермию и другие смешанные формы патозооспермии. Показано, что двунитевые разрывы ДНК составляют большую долю (в среднем около 44–50 %) от общего количества повреждений ДНК (однои двунитевых разрывов, щелочно-лабильных сайтов и др.), регистрируемых с использованием щелочной версии метода ДНК-комет, рекомендованной Всемирной организацией здравоохранения. Установлены более высокие уровни двунитевых разрывов ДНК спермиев в группе с патозооспермией и подгруппе с астенозооспермией, чем при нормозооспермии. Показано также, что зарегистрированные при патозооспермии уровни двунитевых разрывов соответствуют мутагенному эффекту in vitro высоких концентраций (10–30 мкг/мл) мощного радиомиметика сульфата блеомицина, что свидетельствует о существенном нарушении целостности ДНК при патозооспермии. В целом полученные данные говорят о возможности использования анализа двунитевых разрывов ДНК спермиев в диагностике мужского бесплодия

Geographical Distribution, Incidence, Malignancies, and Outcome of 136 Eastern Slavic Patients With Nijmegen Breakage Syndrome and NBN Founder Variant c.657_661del5

Nijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to lymphoid malignancies. The majority of NBS patients are identified with a homozygous five base pair deletion in the Nibrin (NBN) gene (c.657_661del5, p.K219fsX19) with a founder effect observed in Caucasian European populations, especially of Slavic origin. We present here an analysis of a cohort of 136 NBS patients of Eastern Slav origin across Belarus, Ukraine, Russia, and Latvia with a focus on understanding the geographic distribution, incidence of malignancy, and treatment outcomes of this cohort. Our analysis shows that Belarus had the highest prevalence of NBS (2.3 per 1,000,000), followed by Ukraine (1.3 per 1,000,000), and Russia (0.7 per 1,000,000). Of note, the highest concentration of NBS cases was observed in the western regions of Belarus and Ukraine, where NBS prevalence exceeds 20 cases per 1,000,000 people, suggesting the presence of an “Eastern Slavic NBS hot spot.” The median age at diagnosis of this cohort ranged from 4 to 5 years, and delay in diagnosis was more pervasive in smaller cities and rural regions. A total of 62 (45%) patients developed malignancies, more commonly in males than females (55.2 vs. 34.2%; p=0.017). In 27 patients, NBS was diagnosed following the onset of malignancies (mean age: 8 years). Malignancies were mostly of lymphoid origin and predominantly non-Hodgkin lymphoma (NHL) (n=42, 68%); 38% of patients had diffuse large B-cell lymphoma. The 20-year overall survival rate of patients with malignancy was 24%. However, females with cancer experienced poorer event-free survival rates than males (16.6% vs. 46.8%, p=0.036). Of 136 NBS patients, 13 underwent hematopoietic stem cell transplantation (HSCT) with an overall survival of 3.5 years following treatment (range: 1 to 14 years). Indications for HSCT included malignancy (n=7) and immunodeficiency (n=6). Overall, 9% of patients in this cohort reached adulthood. Adult survivors reported diminished quality of life with significant physical and cognitive impairments. Our study highlights the need to improve timely diagnosis and clinical management of NBS among Eastern Slavs. Genetic counseling and screening should be offered to individuals with a family history of NBS, especially in hot spot regions. © Copyright © 2021 Sharapova, Pashchenko, Bondarenko, Vakhlyarskaya, Prokofjeva, Fedorova, Savchak, Mareika, Valiev, Popa, Tuzankina, Vlasova, Sakovich, Polyakova, Rumiantseva, Naumchik, Kulyova, Aleshkevich, Golovataya, Minakovskaya, Belevtsev, Latysheva, Latysheva, Beznoshchenko, Akopyan, Makukh, Kozlova, Varabyou, Ballow, Ong, Walter, Kondratenko, Kostyuchenko and Aleinikova.We thank all doctors for clinical help for patients. We also appreciate the support of patient and their parents for agreeing to take part in this study. TP thanks Sergey?Nikulshin, Marika Grutupa, and Zanna Kovalova. We thank Joseph Dasso for editing this manuscript, primarily for proper English

Первый опыт успешного вынашивания беременности после симультанной трансплантации печени и почки с рено-портальной транспозицией

The article is dedicated to the problem of pregnancy management and delivery after simultaneous liver-kidney transplantation (SLKT). The article contains general historic and statistic information, and presents the first real world clinical case of favorable pregnancy outcome in patient after simultaneous liver-kidney transplantation with reno-portal transposition.Статья посвящена вопросу ведения беременности и родоразрешения после симультанной трансплантации печени и почки (СТПП). Приведены общие исторические и статистические сведения, и представлен первый в мировой практике клинический случай благоприятного исхода беременности у пациентки после СТПП с рено-портальной транспозицией

First experience in two successful consecutive pregnancies after simultaneous liver-kidney transplantation with reno-portal transposition

The paper presents the world’s first clinical case of two full-term successive pregnancies in a patient following simultaneous liver-kidney transplantation with reno-portal transposition. Both pregnancies ended with the birth of healthy children and favorable course of postpartum and long-term periods. The features of management and childbirth are highlighted. Literature review on this problem is presented

Heteromorphic variants of chromosome 9

BACKGROUND: Heterochromatic variants of pericentromere of chromosome 9 are reported and discussed since decades concerning their detailed structure and clinical meaning. However, detailed studies are scarce. Thus, here we provide the largest ever done molecular cytogenetic research based on >300 chromosome 9 heteromorphism carriers. RESULTS: In this study, 334 carriers of heterochromatic variants of chromosome 9 were included, being 192 patients from Western Europe and the remainder from Easter-European origin. A 3-color-fluorescence in situ hybridization (FISH) probe-set directed against for 9p12 to 9q13~21.1 (9het-mix) and 8 different locus-specific probes were applied for their characterization. The 9het-mix enables the characterization of 21 of the yet known 24 chromosome 9 heteromorphic patterns. In this study, 17 different variants were detected including five yet unreported; the most frequent were pericentric inversions (49.4%) followed by 9qh-variants (23.9%), variants of 9ph (11.4%), cenh (8.2%), and dicentric- (3.8%) and duplication-variants (3.3%). For reasons of simplicity, a new short nomenclature for the yet reported 24 heteromorphic patterns of chromosome 9 is suggested. Six breakpoints involved in four of the 24 variants could be narrowed down using locus-specific probes. CONCLUSIONS: Based on this largest study ever done in carriers of chromosome 9 heteromorphisms, three of the 24 detailed variants were more frequently observed in Western than in Eastern Europe. Besides, there is no clear evidence that infertility is linked to any of the 24 chromosome 9 heteromorphic variants