Geographical Distribution, Incidence, Malignancies, and Outcome of 136 Eastern Slavic Patients With Nijmegen Breakage Syndrome and NBN Founder Variant c.657_661del5
| Autor: | Ihor Savchak, Irina A. Tuzankina, E.A. Latysheva, Halyna Makukh, Anastasiia Bondarenko, Mikhail Belevtsev, Inga S. Sakovich, Elena I. Golovataya, Svetlana A. Kulyova, Larysa Kostyuchenko, Jolan E. Walter, Alexander Popa, Dzmitry S. Varabyou, Natalia V. Rumiantseva, Mei-Sing Ong, Alexander G. Beznoshchenko, Svetlana S. Vakhlyarskaya, Mark Ballow, Ekaterina A. Polyakova, Olga E. Pashchenko, Olga Aleinikova, Yuliya Mareika, Svetlana Aleshkevich, Elena V. Vlasova, Olena Kozlova, Svetlana O. Sharapova, Irina V. Naumchik, Nina V. Minakovskaya, Hayane Akopyan, Timur T. Valiev, Alina Fedorova, Tatjana Prokofjeva, Tatiana V. Latysheva, Irina Kondratenko |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Pediatrics GEOGRAPHIC DISTRIBUTION medicine.medical_treatment NONHODGKIN LYMPHOMA LYMPHOPROLIFERATIVE DISORDERS EASTERN EUROPE Hematopoietic stem cell transplantation MAJOR CLINICAL STUDY ADOLESCENT lymphomas risk of malignancies IMMUNOLOGY Nijmegen breakage syndrome (NBS) NUCLEAR PROTEIN 0302 clinical medicine CHILD EVENT FREE SURVIVAL RETROSPECTIVE STUDIES RETROSPECTIVE STUDY NBN PROTEIN HUMAN Immunology and Allergy LYMPHOMAS RISK OF MALIGNANCIES COGNITIVE DEFECT EPIDEMIOLOGY FOUNDER VARIANTS geographical location Family history incidence in East Slavs Immunodeficiency MALIGNANT NEOPLASM Incidence (epidemiology) HUMAN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION HEALTH CARE SURVEY HEMATOPOIETIC STEM CELL TRANSPLANTATION CLINICAL TRIAL HUMANS INCIDENCE IN EAST SLAVS HEMATOLOGIC NEOPLASMS FOUNDER EFFECT FEMALE LYMPHOPROLIFERATIVE DISEASE PREVALENCE SOCIAL ADAPTATION IMMUNE DEFICIENCY FOLLOW UP MENTAL HEALTH Cohort HEMATOLOGIC DISEASE B CELL LYMPHOMA CANCER SURVIVAL HODGKIN DISEASE lcsh:Immunologic diseases. Allergy medicine.medical_specialty NIJMEGEN BREAKAGE SYNDROME GENETICS Genetic counseling Immunology COHORT ANALYSIS CELL CYCLE PROTEINS Malignancy founder variants 03 medical and health sciences NIJMEGEN BREAKAGE SYNDROME (NBS) QUALITY OF LIFE ADULT GEOGRAPHICAL LOCATION medicine ARTICLE CELL CYCLE PROTEIN CHILD PRESCHOOL FOLLOW-UP STUDIES MALE business.industry MORTALITY ACUTE LYMPHOBLASTIC LEUKEMIA social adaptation medicine.disease NIBRIN 030104 developmental biology BURKITT LYMPHOMA OVERALL SURVIVAL PRESCHOOL CHILD NUCLEAR PROTEINS MULTICENTER STUDY INFANT EUROPE EASTERN business lcsh:RC581-607 Nijmegen breakage syndrome 030215 immunology INCIDENCE |
| Zdroj: | Front. Immunol. Frontiers in Immunology Frontiers in Immunology, Vol 11 (2021) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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