Please use this identifier to cite or link to this item: http://hdl.handle.net/10995/103142
Title: Geographical Distribution, Incidence, Malignancies, and Outcome of 136 Eastern Slavic Patients With Nijmegen Breakage Syndrome and NBN Founder Variant c.657_661del5
Authors: Sharapova, S. O.
Pashchenko, O. E.
Bondarenko, A. V.
Vakhlyarskaya, S. S.
Prokofjeva, T.
Fedorova, A. S.
Savchak, I.
Mareika, Y.
Valiev, T. T.
Popa, A.
Tuzankina, I. A.
Vlasova, E. V.
Sakovich, I. S.
Polyakova, E. A.
Rumiantseva, N. V.
Naumchik, I. V.
Kulyova, S. A.
Aleshkevich, S. N.
Golovataya, E. I.
Minakovskaya, N. V.
Belevtsev, M. V.
Latysheva, E. A.
Latysheva, T. V.
Beznoshchenko, A. G.
Akopyan, H.
Makukh, H.
Kozlova, O.
Varabyou, D. S.
Ballow, M.
Ong, M. -S.
Walter, J. E.
Kondratenko, I. V.
Kostyuchenko, L. V.
Aleinikova, O. V.
Issue Date: 2021
Publisher: Frontiers Media S.A.
Citation: Geographical Distribution, Incidence, Malignancies, and Outcome of 136 Eastern Slavic Patients With Nijmegen Breakage Syndrome and NBN Founder Variant c.657_661del5 / S. O. Sharapova, O. E. Pashchenko, A. V. Bondarenko, et al. — DOI 10.3389/fimmu.2020.602482 // Frontiers in Immunology. — 2021. — Vol. 11. — 602482.
Abstract: 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.
Keywords: FOUNDER VARIANTS
GEOGRAPHICAL LOCATION
INCIDENCE IN EAST SLAVS
LYMPHOMAS, RISK OF MALIGNANCIES
NIJMEGEN BREAKAGE SYNDROME (NBS)
QUALITY OF LIFE
SOCIAL ADAPTATION
NIBRIN
CELL CYCLE PROTEIN
NBN PROTEIN, HUMAN
NUCLEAR PROTEIN
ACUTE LYMPHOBLASTIC LEUKEMIA
ADULT
ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
ARTICLE
B CELL LYMPHOMA
BURKITT LYMPHOMA
CANCER SURVIVAL
CHILD
COGNITIVE DEFECT
COHORT ANALYSIS
EVENT FREE SURVIVAL
FEMALE
GEOGRAPHIC DISTRIBUTION
HEALTH CARE SURVEY
HEMATOPOIETIC STEM CELL TRANSPLANTATION
HODGKIN DISEASE
HUMAN
IMMUNE DEFICIENCY
INCIDENCE
INFANT
MAJOR CLINICAL STUDY
MALE
MALIGNANT NEOPLASM
MENTAL HEALTH
MULTICENTER STUDY
NIJMEGEN BREAKAGE SYNDROME
NONHODGKIN LYMPHOMA
OVERALL SURVIVAL
QUALITY OF LIFE
RETROSPECTIVE STUDY
ADOLESCENT
CLINICAL TRIAL
EASTERN EUROPE
EPIDEMIOLOGY
FOLLOW UP
FOUNDER EFFECT
GENETICS
HEMATOLOGIC DISEASE
IMMUNOLOGY
INCIDENCE
LYMPHOPROLIFERATIVE DISEASE
MORTALITY
NIJMEGEN BREAKAGE SYNDROME
PRESCHOOL CHILD
PREVALENCE
ADOLESCENT
ADULT
CELL CYCLE PROTEINS
CHILD
CHILD, PRESCHOOL
EUROPE, EASTERN
FEMALE
FOLLOW-UP STUDIES
FOUNDER EFFECT
HEMATOLOGIC NEOPLASMS
HUMANS
INCIDENCE
LYMPHOPROLIFERATIVE DISORDERS
MALE
NIJMEGEN BREAKAGE SYNDROME
NUCLEAR PROTEINS
PREVALENCE
QUALITY OF LIFE
RETROSPECTIVE STUDIES
URI: http://hdl.handle.net/10995/103142
Access: info:eu-repo/semantics/openAccess
SCOPUS ID: 85099742187
PURE ID: 20904950
530d1999-2982-49c2-a321-850050cebaf7
ISSN: 16643224
DOI: 10.3389/fimmu.2020.602482
metadata.dc.description.sponsorship: 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.
Appears in Collections:Научные публикации, проиндексированные в SCOPUS и WoS CC

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