Log in

Relevant bibliographies by topics / Cernunnos-XLF / Journal articles

To see the other types of publications on this topic, follow the link: Cernunnos-XLF.

Journal articles on the topic 'Cernunnos-XLF'

Author: Grafiati

Published: 7 September 2022

Last updated: 18 September 2022

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the top 32 journal articles for your research on the topic 'Cernunnos-XLF.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.

1

Malivert, Laurent, Isabelle Callebaut, Paola Rivera-Munoz, Alain Fischer, Jean-Paul Mornon, Patrick Revy, and Jean-Pierre de Villartay. "The C-Terminal Domain of Cernunnos/XLF Is Dispensable for DNA Repair In Vivo." Molecular and Cellular Biology 29, no. 5 (December 22, 2008): 1116–22. http://dx.doi.org/10.1128/mcb.01521-08.

Full text

Abstract:

ABSTRACT The core nonhomologous end-joining DNA repair pathway is composed of seven factors: Ku70, Ku80, DNA-PKcs, Artemis, XRCC4 (X4), DNA ligase IV (L4), and Cernunnos/XLF (Cernunnos). Although Cernunnos and X4 are structurally related and participate in the same complex together with L4, they have distinct functions during DNA repair. L4 relies on X4 but not on Cernunnos for its stability, and L4 is required for optimal interaction of Cernunnos with X4. We demonstrate here, using in vitro-generated Cernunnos mutants and a series of functional assays in vivo, that the C-terminal region of Cernunnos is dispensable for its activity during DNA repair.

APA, Harvard, Vancouver, ISO, and other styles

2

Çipe, Funda Erol, Cigdem Aydogmus, Arzu Babayigit Hocaoglu, Merve Kilic, Gul Demet Kaya, and Elif Yilmaz Gulec. "Cernunnos/XLF Deficiency: A Syndromic Primary Immunodeficiency." Case Reports in Pediatrics 2014 (2014): 1–4. http://dx.doi.org/10.1155/2014/614238.

Full text

Abstract:

Artemis, DNA ligase IV, DNA protein kinase catalytic subunit, and Cernunnos/XLF genes in nonhomologous end joining pathways of DNA repair mechanisms have been identified as responsible for radiosensitive SCID. Here, we present a 3-year-old girl patient with severe growth retardation, bird-like face, recurrent perianal abscess, pancytopenia, and polydactyly. Firstly, she was thought as Fanconi anemia and spontaneous DNA breaks were seen on chromosomal analysis. After that DEB test was found to be normal and Fanconi anemia was excluded. Because of that she had low IgG and IgA levels, normal IgM level, and absence of B cells in peripheral blood; she was considered as primary immunodeficiency, Nijmegen breakage syndrome. A mutation in NBS1 gene was not found; then Cernunnos/XLF deficiency was investigated due to clinical similarities with previously reported cases. Homozygous mutation in Cernunnos/XLF gene (NHEJ1) was identified. She is now on regular IVIG prophylaxis and has no new infection. Fully matched donor screening is in progress for bone marrow transplantation which is curative treatment of the disease. In conclusion, the patients with microcephaly, bird-like face, and severe growth retardation should be evaluated for hypogammaglobulinemia and primary immunodeficiency diseases.

APA, Harvard, Vancouver, ISO, and other styles

3

Musilli, Stefania, Vincent Abramowski, Benoit Roch, and Jean-Pierre de Villartay. "An in vivo study of the impact of deficiency in the DNA repair proteins PAXX and XLF on development and maturation of the hemolymphoid system." Journal of Biological Chemistry 295, no. 8 (January 8, 2020): 2398–406. http://dx.doi.org/10.1074/jbc.ac119.010924.

Full text

Abstract:

Repair of DNA double-strand breaks by the nonhomologous end joining pathway is central for proper development of the adaptive immune system. This repair pathway involves eight factors, including XRCC4-like factor (XLF)/Cernunnos and the paralog of XRCC4 and XLF, PAXX nonhomologous end joining factor (PAXX). Xlf−/− and Paxx−/− mice are viable and exhibit only a mild immunophenotype. However, mice lacking both PAXX and XLF are embryonic lethal because postmitotic neurons undergo massive apoptosis in embryos. To decipher the roles of PAXX and XLF in both variable, diversity, and joining recombination and immunoglobulin class switch recombination, here, using Cre/lox-specific deletion to prevent double-KO embryonic lethality, we developed two mouse models of a conditional Xlf KO in a Paxx−/− background. Cre expressed under control of the iVav or CD21 promoter enabled Xlf deletion in early hematopoietic progenitors and splenic mature B cells, respectively. We demonstrate the XLF and PAXX interplay during variable, diversity, and joining recombination in vivo but not during class switch recombination, for which PAXX appeared to be fully dispensable. Xlf/Paxx double KO in hematopoietic progenitors resulted in a shorter lifespan associated with onset of thymic lymphomas, revealing a genome caretaking function of XLF/PAXX.

APA, Harvard, Vancouver, ISO, and other styles

4

Avagyan, Serine, Michael Churchill, Kenta Yamamoto, Jennifer L. Crowe, Chen Li, Brian J. Lee, Tian Zheng, Siddhartha Mukherjee, and Shan Zha. "Hematopoietic stem cell dysfunction underlies the progressive lymphocytopenia in XLF/Cernunnos deficiency." Blood 124, no. 10 (September 4, 2014): 1622–25. http://dx.doi.org/10.1182/blood-2014-05-574863.

Full text

Abstract:

Key Points XLF-deficient mice recapitulate the lymphocytopenia of XLF-deficient patients. Premature aging of hematopoietic stem cells underlies the severe and progressive lymphocytopenia in XLF-deficient mice.

APA, Harvard, Vancouver, ISO, and other styles

5

Faraci, Maura, Edoardo Lanino, Concetta Micalizzi, Giuseppe Morreale, Daniela Di Martino, Laura Banov, Patrizia Comoli, Franco Locatelli, Annarosa Soresina, and Alessandro Plebani. "Unrelated hematopoietic stem cell transplantation for Cernunnos-XLF deficiency." Pediatric Transplantation 13, no. 6 (September 2009): 785–89. http://dx.doi.org/10.1111/j.1399-3046.2008.01028.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

6

Mahaney, Brandi L., Michal Hammel, Katheryn Meek, John A. Tainer, and Susan P. Lees-Miller. "XRCC4 and XLF form long helical protein filaments suitable for DNA end protection and alignment to facilitate DNA double strand break repair." Biochemistry and Cell Biology 91, no. 1 (February 2013): 31–41. http://dx.doi.org/10.1139/bcb-2012-0058.

Full text

Abstract:

DNA double strand breaks (DSBs), induced by ionizing radiation (IR) and endogenous stress including replication failure, are the most cytotoxic form of DNA damage. In human cells, most IR-induced DSBs are repaired by the nonhomologous end joining (NHEJ) pathway. One of the most critical steps in NHEJ is ligation of DNA ends by DNA ligase IV (LIG4), which interacts with, and is stabilized by, the scaffolding protein X-ray cross-complementing gene 4 (XRCC4). XRCC4 also interacts with XRCC4-like factor (XLF, also called Cernunnos); yet, XLF has been one of the least mechanistically understood proteins and precisely how XLF functions in NHEJ has been enigmatic. Here, we examine current combined structural and mutational findings that uncover integrated functions of XRCC4 and XLF and reveal their interactions to form long, helical protein filaments suitable to protect and align DSB ends. XLF–XRCC4 provides a global structural scaffold for ligating DSBs without requiring long DNA ends, thus ensuring accurate and efficient ligation and repair. The assembly of these XRCC4–XLF filaments, providing both DNA end protection and alignment, may commit cells to NHEJ with general biological implications for NHEJ and DSB repair processes and their links to cancer predispositions and interventions.

APA, Harvard, Vancouver, ISO, and other styles

7

Beck, Carole, Sergio Castañeda-Zegarra, Camilla Huse, Mengtan Xing, and Valentyn Oksenych. "Mediator of DNA Damage Checkpoint Protein 1 Facilitates V(D)J Recombination in Cells Lacking DNA Repair Factor XLF." Biomolecules 10, no. 1 (December 30, 2019): 60. http://dx.doi.org/10.3390/biom10010060.

Full text

Abstract:

DNA double-strand breaks (DSBs) trigger the Ataxia telangiectasia mutated (ATM)-dependent DNA damage response (DDR), which consists of histone H2AX, MDC1, RNF168, 53BP1, PTIP, RIF1, Rev7, and Shieldin. Early stages of B and T lymphocyte development are dependent on recombination activating gene (RAG)-induced DSBs that form the basis for further V(D)J recombination. Non-homologous end joining (NHEJ) pathway factors recognize, process, and ligate DSBs. Based on numerous loss-of-function studies, DDR factors were thought to be dispensable for the V(D)J recombination. In particular, mice lacking Mediator of DNA Damage Checkpoint Protein 1 (MDC1) possessed nearly wild-type levels of mature B and T lymphocytes in the spleen, thymus, and bone marrow. NHEJ factor XRCC4-like factor (XLF)/Cernunnos is functionally redundant with ATM, histone H2AX, and p53-binding protein 1 (53BP1) during the lymphocyte development in mice. Here, we genetically inactivated MDC1, XLF, or both MDC1 and XLF in murine vAbl pro-B cell lines and, using chromosomally integrated substrates, demonstrated that MDC1 stimulates the V(D)J recombination in cells lacking XLF. Moreover, combined inactivation of MDC1 and XLF in mice resulted in synthetic lethality. Together, these findings suggest that MDC1 and XLF are functionally redundant during the mouse development, in general, and the V(D)J recombination, in particular.

APA, Harvard, Vancouver, ISO, and other styles

8

Cottarel, Jessica, Philippe Frit, Oriane Bombarde, Bernard Salles, Aurélie Négrel, Stéphanie Bernard, Penny A. Jeggo, Michael R. Lieber, Mauro Modesti, and Patrick Calsou. "A noncatalytic function of the ligation complex during nonhomologous end joining." Journal of Cell Biology 200, no. 2 (January 21, 2013): 173–86. http://dx.doi.org/10.1083/jcb.201203128.

Full text

Abstract:

Nonhomologous end joining is the primary deoxyribonucleic acid (DNA) double-strand break repair pathway in multicellular eukaryotes. To initiate repair, Ku binds DNA ends and recruits the DNA-dependent protein kinase (DNA-PK) catalytic subunit (DNA-PKcs) forming the holoenzyme. Early end synapsis is associated with kinase autophosphorylation. The XRCC4 (X4)–DNA Ligase IV (LIG4) complex (X4LIG4) executes the final ligation promoted by Cernunnos (Cer)–X4-like factor (XLF). In this paper, using a cell-free system that recapitulates end synapsis and DNA-PKcs autophosphorylation, we found a defect in both activities in human cell extracts lacking LIG4. LIG4 also stimulated the DNA-PKcs autophosphorylation in a reconstitution assay with purified components. We additionally uncovered a kinase autophosphorylation defect in LIG4-defective cells that was corrected by ectopic expression of catalytically dead LIG4. Finally, our data support a contribution of Cer-XLF to this unexpected early role of the ligation complex in end joining. We propose that productive end joining occurs by early formation of a supramolecular entity containing both DNA-PK and X4LIG4–Cer-XLF complexes on DNA ends.

APA, Harvard, Vancouver, ISO, and other styles

9

Tsai, C. J., S. A. Kim, and G. Chu. "Cernunnos/XLF promotes the ligation of mismatched and noncohesive DNA ends." Proceedings of the National Academy of Sciences 104, no. 19 (April 30, 2007): 7851–56. http://dx.doi.org/10.1073/pnas.0702620104.

Full text

APA, Harvard, Vancouver, ISO, and other styles

10

Riballo, Enriqueta, Lisa Woodbine, Thomas Stiff, Sarah A. Walker, Aaron A. Goodarzi, and Penny A. Jeggo. "XLF-Cernunnos promotes DNA ligase IV–XRCC4 re-adenylation following ligation." Nucleic Acids Research 37, no. 2 (December 4, 2008): 482–92. http://dx.doi.org/10.1093/nar/gkn957.

Full text

APA, Harvard, Vancouver, ISO, and other styles

11

Yano, Ken-ichi, Keiko Morotomi-Yano, and Hidenori Akiyama. "Cernunnos/XLF: A new player in DNA double-strand break repair." International Journal of Biochemistry & Cell Biology 41, no. 6 (June 2009): 1237–40. http://dx.doi.org/10.1016/j.biocel.2008.10.005.

Full text

APA, Harvard, Vancouver, ISO, and other styles

12

Ochi, Takashi, Bancinyane Lynn Sibanda, Qian Wu, Dimitri Y. Chirgadze, Victor M. Bolanos-Garcia, and Tom L. Blundell. "Structural Biology of DNA Repair: Spatial Organisation of the Multicomponent Complexes of Nonhomologous End Joining." Journal of Nucleic Acids 2010 (2010): 1–19. http://dx.doi.org/10.4061/2010/621695.

Full text

Abstract:

Nonhomologous end joining (NHEJ) plays a major role in double-strand break DNA repair, which involves a series of steps mediated by multiprotein complexes. A ring-shaped Ku70/Ku80 heterodimer forms first at broken DNA ends, DNA-dependent protein kinase catalytic subunit (DNA-PKcs) binds to mediate synapsis and nucleases process DNA overhangs. DNA ligase IV (LigIV) is recruited as a complex with XRCC4 for ligation, with XLF/Cernunnos, playing a role in enhancing activity of LigIV. We describe how a combination of methods—X-ray crystallography, electron microscopy and small angle X-ray scattering—can give insights into the transient multicomponent complexes that mediate NHEJ. We first consider the organisation of DNA-PKcs/Ku70/Ku80/DNA complex (DNA-PK) and then discuss emerging evidence concerning LigIV/XRCC4/XLF/DNA and higher-order complexes. We conclude by discussing roles of multiprotein systems in maintaining high signal-to-noise and the value of structural studies in developing new therapies in oncology and elsewhere.

APA, Harvard, Vancouver, ISO, and other styles

13

Schwartz, Michal, Yifat S. Oren, Assaf C. Bester, Ayelet Rahat, Ruthy Sfez, Shlomo Yitzchaik, Jean-Pierre de Villartay, and Batsheva Kerem. "Impaired Replication Stress Response in Cells from Immunodeficiency Patients Carrying Cernunnos/XLF Mutations." PLoS ONE 4, no. 2 (February 18, 2009): e4516. http://dx.doi.org/10.1371/journal.pone.0004516.

Full text

APA, Harvard, Vancouver, ISO, and other styles

14

Çağdaş, Deniz, Tuba Turul Özgür, Gülten Türkkanı Asal, Patrick Revy, Jean-Pierre De Villartay, Mirjam van der Burg, Özden Sanal, and İlhan Tezcan. "Two SCID cases with Cernunnos-XLF deficiency successfully treated by hematopoietic stem cell transplantation." Pediatric Transplantation 16, no. 5 (April 27, 2011): E167—E171. http://dx.doi.org/10.1111/j.1399-3046.2011.01491.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

15

Malivert, Laurent, Virginie Ropars, Marcela Nunez, Pascal Drevet, Simona Miron, Guilhem Faure, Raphael Guerois, et al. "Delineation of the Xrcc4-interacting Region in the Globular Head Domain of Cernunnos/XLF." Journal of Biological Chemistry 285, no. 34 (June 17, 2010): 26475–83. http://dx.doi.org/10.1074/jbc.m110.138156.

Full text

APA, Harvard, Vancouver, ISO, and other styles

16

Zha, S., F. W. Alt, H. L. Cheng, J. W. Brush, and G. Li. "Defective DNA repair and increased genomic instability in Cernunnos-XLF-deficient murine ES cells." Proceedings of the National Academy of Sciences 104, no. 11 (March 7, 2007): 4518–23. http://dx.doi.org/10.1073/pnas.0611734104.

Full text

APA, Harvard, Vancouver, ISO, and other styles

17

Li, Gang, Frederick W. Alt, Hwei-Ling Cheng, James W. Brush, Peter H. Goff, Mike M. Murphy, Sonia Franco, Yu Zhang, and Shan Zha. "Lymphocyte-Specific Compensation for XLF/Cernunnos End-Joining Functions in V(D)J Recombination." Molecular Cell 31, no. 5 (September 2008): 631–40. http://dx.doi.org/10.1016/j.molcel.2008.07.017.

Full text

APA, Harvard, Vancouver, ISO, and other styles

18

Hentges, Pierre, Peter Ahnesorg, Robert S. Pitcher, Chris K. Bruce, Boris Kysela, Andrew J. Green, Julie Bianchi, Thomas E. Wilson, Stephen P. Jackson, and Aidan J. Doherty. "Evolutionary and Functional Conservation of the DNA Non-homologous End-joining Protein, XLF/Cernunnos." Journal of Biological Chemistry 281, no. 49 (October 12, 2006): 37517–26. http://dx.doi.org/10.1074/jbc.m608727200.

Full text

APA, Harvard, Vancouver, ISO, and other styles

19

Li, Yi, Dimitri Y. Chirgadze, Victor M. Bolanos-Garcia, Bancinyane L. Sibanda, Owen R. Davies, Peter Ahnesorg, Stephen P. Jackson, and Tom L. Blundell. "Crystal structure of human XLF/Cernunnos reveals unexpected differences from XRCC4 with implications for NHEJ." EMBO Journal 27, no. 1 (November 29, 2007): 290–300. http://dx.doi.org/10.1038/sj.emboj.7601942.

Full text

APA, Harvard, Vancouver, ISO, and other styles

20

Wu, Peï-Yu, Philippe Frit, Laurent Malivert, Patrick Revy, Denis Biard, Bernard Salles, and Patrick Calsou. "Interplay between Cernunnos-XLF and Nonhomologous End-joining Proteins at DNA Ends in the Cell." Journal of Biological Chemistry 282, no. 44 (August 24, 2007): 31937–43. http://dx.doi.org/10.1074/jbc.m704554200.

Full text

APA, Harvard, Vancouver, ISO, and other styles

21

Menon, Vijay, and Lawrence F. Povirk. "XLF/Cernunnos: An important but puzzling participant in the nonhomologous end joining DNA repair pathway." DNA Repair 58 (October 2017): 29–37. http://dx.doi.org/10.1016/j.dnarep.2017.08.003.

Full text

APA, Harvard, Vancouver, ISO, and other styles

22

Carrillo, Jaime, Oriol Calvete, Laura Pintado-Berninches, Cristina Manguan-García, Julian Sevilla Navarro, Elena G. Arias-Salgado, Leandro Sastre, et al. "Mutations in XLF/NHEJ1/Cernunnos gene results in downregulation of telomerase genes expression and telomere shortening." Human Molecular Genetics 26, no. 10 (March 24, 2017): 1900–1914. http://dx.doi.org/10.1093/hmg/ddx098.

Full text

APA, Harvard, Vancouver, ISO, and other styles

23

Ropars, V., P. Drevet, P. Legrand, S. Baconnais, J. Amram, G. Faure, J. A. Marquez, et al. "Structural characterization of filaments formed by human Xrcc4-Cernunnos/XLF complex involved in nonhomologous DNA end-joining." Proceedings of the National Academy of Sciences 108, no. 31 (July 18, 2011): 12663–68. http://dx.doi.org/10.1073/pnas.1100758108.

Full text

APA, Harvard, Vancouver, ISO, and other styles

24

Revy, Patrick, Laurent Malivert, and Jean-Pierre de Villartay. "Cernunnos-XLF, a recently identified non-homologous end-joining factor required for the development of the immune system." Current Opinion in Allergy and Clinical Immunology 6, no. 6 (December 2006): 416–20. http://dx.doi.org/10.1097/01.all.0000246623.72365.43.

Full text

APA, Harvard, Vancouver, ISO, and other styles

25

Mahaney, Brandi L., Katheryn Meek, and Susan P. Lees-Miller. "Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining." Biochemical Journal 417, no. 3 (January 16, 2009): 639–50. http://dx.doi.org/10.1042/bj20080413.

Full text

Abstract:

DNA DSBs (double-strand breaks) are considered the most cytotoxic type of DNA lesion. They can be introduced by external sources such as IR (ionizing radiation), by chemotherapeutic drugs such as topoisomerase poisons and by normal biological processes such as V(D)J recombination. If left unrepaired, DSBs can cause cell death. If misrepaired, DSBs may lead to chromosomal translocations and genomic instability. One of the major pathways for the repair of IR-induced DSBs in mammalian cells is NHEJ (non-homologous end-joining). The main proteins required for NHEJ in mammalian cells are the Ku heterodimer (Ku70/80 heterodimer), DNA-PKcs [the catalytic subunit of DNA-PK (DNA-dependent protein kinase)], Artemis, XRCC4 (X-ray-complementing Chinese hamster gene 4), DNA ligase IV and XLF (XRCC4-like factor; also called Cernunnos). Additional proteins, including DNA polymerases μ and λ, PNK (polynucleotide kinase) and WRN (Werner's Syndrome helicase), may also play a role. In the present review, we will discuss our current understanding of the mechanism of NHEJ in mammalian cells and discuss the roles of DNA-PKcs and DNA-PK-mediated phosphorylation in NHEJ.

APA, Harvard, Vancouver, ISO, and other styles

26

YU, Y., B. MAHANEY, K. YANO, R. YE, S. FANG, P. DOUGLAS, D. CHEN, and S. LEESMILLER. "DNA-PK and ATM phosphorylation sites in XLF/Cernunnos are not required for repair of DNA double strand breaks." DNA Repair 7, no. 10 (October 1, 2008): 1680–92. http://dx.doi.org/10.1016/j.dnarep.2008.06.015.

Full text

APA, Harvard, Vancouver, ISO, and other styles

27

Akopiants, Konstantin, Rui-Zhe Zhou, Susovan Mohapatra, Kristoffer Valerie, Susan P. Lees-Miller, Kyung-Jong Lee, David J. Chen, Patrick Revy, Jean-Pierre de Villartay, and Lawrence F. Povirk. "Requirement for XLF/Cernunnos in alignment-based gap filling by DNA polymerases λ and μ for nonhomologous end joining in human whole-cell extracts." Nucleic Acids Research 37, no. 12 (May 6, 2009): 4055–62. http://dx.doi.org/10.1093/nar/gkp283.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

Tilgner, Katarzyna, Irina Neganova, Chatchawan Singhapol, Gabriele Saretzki, Jumana Yousuf Al-Aama, Jerome Evans, Vera Gorbunova, et al. "Brief report: A human induced pluripotent stem cell model of cernunnos deficiency reveals an important role for XLF in the survival of the primitive hematopoietic progenitors." STEM CELLS 31, no. 9 (September 2013): 2015–23. http://dx.doi.org/10.1002/stem.1456.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

Bery, Amandine, Olivier Etienne, Laura Mouton, Sofiane Mokrani, Christine Granotier-Beckers, Laurent R. Gauthier, Justyne Feat-Vetel, et al. "XLF/Cernunnos Loss Impairs Mouse Brain Development by Altering Symmetric Proliferative Divisions of Neural Progenitors." SSRN Electronic Journal, 2020. http://dx.doi.org/10.2139/ssrn.3748742.

Full text

APA, Harvard, Vancouver, ISO, and other styles

30

Roch, Benoit, Vincent Abramowski, Julie Chaumeil, and Jean-Pierre de Villartay. "Cernunnos/Xlf Deficiency Results in Suboptimal V(D)J Recombination and Impaired Lymphoid Development in Mice." Frontiers in Immunology 10 (March 14, 2019). http://dx.doi.org/10.3389/fimmu.2019.00443.

Full text

APA, Harvard, Vancouver, ISO, and other styles

31

Lescale, Chloé, Vincent Abramowski, Marie Bedora-Faure, Valentine Murigneux, Gabriella Vera, David B. Roth, Patrick Revy, Jean-Pierre de Villartay, and Ludovic Deriano. "RAG2 and XLF/Cernunnos interplay reveals a novel role for the RAG complex in DNA repair." Nature Communications 7, no. 1 (February 2, 2016). http://dx.doi.org/10.1038/ncomms10529.

Full text

APA, Harvard, Vancouver, ISO, and other styles

32

Frizinsky, Shirly, Erez Rechavi, Ortal Barel, Yu Nee Lee, Amos J. Simon, Atar Lev, Tali Stauber, Etai Adam, and Raz Somech. "Novel NHEJ1 pathogenic variant linked to severe combined immunodeficiency, microcephaly, and abnormal T and B cell receptor repertoires." Frontiers in Pediatrics 10 (July 27, 2022). http://dx.doi.org/10.3389/fped.2022.883173.

Full text

Abstract:

BackgroundDuring the process of generating diverse T and B cell receptor (TCR and BCR, respectively) repertoires, double-strand DNA breaks are produced. Subsequently, these breaks are corrected by a complex system led by the non-homologous end-joining (NHEJ). Pathogenic variants in genes involved in this process, such as the NHEJ1 gene, cause severe combined immunodeficiency syndrome (SCID) along with neurodevelopmental disease and sensitivity to ionizing radiation.ObjectiveTo provide new clinical and immunological insights on NHEJ1 deficiency arising from a newly diagnosed patient with severe immunodeficiency.Materials and methodsA male infant, born to consanguineous parents, suspected of having primary immunodeficiency underwent immunological and genetic workup. This included a thorough assessment of T cell phenotyping and lymphocyte activation by mitogen stimulation tests, whole-exome sequencing (WES), TCR repertoire Vβ repertoire via flow cytometry analysis, and TCR and BCR repertoire analysis via next-generation sequencing (NGS).ResultsClinical findings included microcephaly, recurrent pneumonia, and failure to thrive. An immune workup revealed lymphopenia, reduced T cell function, and hypogammaglobulinemia. Skewed TCR Vβ repertoire, TCR gamma (TRG) repertoire, and BCR repertoire were determined in the patient. Genetic analysis identified a novel homozygous missense pathogenic variant in XLF/Cernunnos: c.A580Ins.T; p.M194fs. The patient underwent a successful hematopoietic stem cell transplantation (HSCT).ConclusionA novel NHEJ1 pathogenic variant is reported in a patient who presented with SCID phenotype that displayed clonally expanded T and B cells. An adjusted HSCT was safe to ensure full T cell immune reconstitution.

APA, Harvard, Vancouver, ISO, and other styles

We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!