Article
Biochemistry & Molecular Biology
Jian Qin, Alexandre Garus, Chantal Autexier
Summary: This study reveals that mutations in the C-terminal extension (CTE) of dyskerin impair its interaction with hTR, leading to X-linked dyskeratosis congenita (X-DC) and related telomere syndromes. These mutations result in reduced binding to SHQ1 and defective binding to hTR. Furthermore, deletion of the CTE further reduces binding to hTR and disrupts the localization and interaction of dyskerin with other molecules.
HUMAN MOLECULAR GENETICS
(2023)
Article
Multidisciplinary Sciences
Chiara Pederiva, Davide M. Trevisan, Dimitra Peirasmaki, Shan Chen, Sharon A. Savage, Ola Larsson, Jernej Ule, Laura Baranello, Federico Agostini, Marianne Farnebo
Summary: Posttranscriptional modifications of mRNA, including pseudouridylation, play a crucial role in gene expression regulation. In this study, dyskerin, a pseudouridine synthase, was found to bind to RNA polymerase II and be responsible for pseudouridylation of thousands of mRNAs. Dyskerin-mediated pseudouridylation was shown to interfere with translation and reduction of the modification led to enhanced protein synthesis. Furthermore, dyskeratosis congenita patients with mutations in the dyskerin-encoding gene showed severe reduction in mRNA pseudouridylation.
Article
Biochemistry & Molecular Biology
Neha Nagpal, Albert K. Tai, Jayakrishnan Nandakumar, Suneet Agarwal
Summary: Mutations in the DKC1 gene lead to abnormalities in scaRNA13, which can be restored by gene editing to repair mutations or inhibition of relevant enzymes; additionally, it was found that the NTE plays an important role in regulating the 3' end definition of snoRNA.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Daniela Maiello, Marianna Varone, Rosario Vicidomini, Valentina Belli, Marina De Rosa, Paola Dama, Maria Furia, Mimmo Turano
Summary: In this paper, the authors investigate the effects of dyskerin depletion on cellular physiology and reveal that dyskerin depletion induces the accumulation of unfolded/misfolded proteins in the endoplasmic reticulum and activates the PERK branch of the unfolded protein response. They also demonstrate that dyskerin downregulation triggers a functional autophagic flux through the inhibition of the PI3K/AKT/mTOR pathway.
Article
Multidisciplinary Sciences
Jesus Garcia-Castillo, Francisca Alcaraz-Perez, Elena Martinez-Balsalobre, Diana Garcia-Moreno, Marlies P. Rossmann, Miriam Fernandez-Lajarin, Manuel Bernabe-Garcia, Ana B. Perez-Oliva, Virginia C. Rodriguez-Cortez, Clara Bueno, Isaac Adatto, Suneet Agarwal, Pablo Menendez, Leonard Zon, Victoriano Mulero, Maria L. Cayuela
Summary: Dyskeratosis congenita (DC) is a rare genetic syndrome caused by mutations in telomerase or telomeric proteins. Research shows that zebrafish terc plays a crucial role in regulating the expression of master myeloid genes, while mutations found in DC patients affect this process.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Hematology
Christopher R. Reilly, Mikko Myllymaki, Robert Redd, Shilpa Padmanaban, Druha Karunakaran, Valerie Tesmer, Frederick D. Tsai, Christopher J. Gibson, Huma Q. Rana, Liang Zhong, Wael Saber, Stephen R. Spellman, Zhen-Huan Hu, Esther H. Orr, Maxine M. Chen, Immaculata De Vivo, Daniel J. DeAngelo, Corey Cutler, Joseph H. Antin, Donna Neuberg, Judy E. Garber, Jayakrishnan Nandakumar, Suneet Agarwal, R. Coleman Lindsley
Summary: Research indicates that rare TERT variants are associated with an increased risk of developing MDS and nonrelapse mortality, with 90% of the variants showing impairment in telomere elongation function. Routine screening for TERT rare variants in MDS patients may enhance transplant outcomes.
Article
Oncology
Szymon Janczar, Martin Kirschner, Fabian Beier, Tim H. Bruemmendorf, Marek Ussowicz, Katarzyna Babol-Pokora, Aleksandra Oszer, Ayami Yoshimi, Krzysztof Kalwak, Wojciech Mlynarski
Summary: Dyskeratosis congenita is a bone marrow failure syndrome with telomere biology abnormalities. A boy with a rare TERT gene variant presented with juvenile myelomonocytic leukemia.
PEDIATRIC BLOOD & CANCER
(2022)
Article
Genetics & Heredity
Ece Cepni, Nihan Bilge Satkin, Lia Abbasi Moheb, Maria Eugenia Rocha, Hulya Kayserili
Summary: Short telomere syndromes are characterized by short telomeres and impaired telomerase activity due to pathogenic variants, with different clinical conditions. DC is a rare telomere biology disorder with skin abnormalities and oral/nail issues, while HHS is an autosomal recessively inherited subgroup with growth retardation and severe immunodeficiency. A consanguineous family in Turkey was reported to have a missense variant in the TERT gene associated with short telomere lengths and varied manifestations.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Endocrinology & Metabolism
Yanxiu Li, Iokfai Cheang, Zhongwen Zhang, Wenming Yao, Yanli Zhou, Haifeng Zhang, Yun Liu, Xiangrong Zuo, Xinli Li, Quan Cao
Summary: This study found that SNPs of TERC and TERT genes are associated with the prognosis of AHF, with mutant alleles being related to long-term mortality. Significant differences were observed in specific haplotypes, with CCAC being a risk factor and GTGT being a protective factor.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Genetics & Heredity
Dhuha M. B. AlDehaini, Suzanne A. Al-Bustan, Zainab Hasan Abdulla Malalla, Muhalab E. Ali, Mai Sater, Hayder A. Giha
Summary: The research found that leukocytes TL (LTL) are significantly shortened in type 2 diabetes patients, but this is not due to TE deficiency or gene polymorphisms. The plasma TE levels are significantly influenced by TERT and ACYP2 gene polymorphisms.
Article
Hematology
Aram Niaz, Jia Truong, Annabel Manoleras, Lucy C. Fox, Piers Blombery, Raja S. Vasireddy, Hilda A. Pickett, Julie A. Curtin, Pasquale M. Barbaro, Jonathan Rodgers, John Roy, Lisa G. Riley, Jessica K. Holien, Scott B. Cohen, Tracy M. Bryan
Summary: Telomere biology disorders (TBDs) are inherited disorders characterized by bone marrow failure. This study investigated a patient with compound heterozygous variants in the TERT gene and found functional interaction between the proteins encoded by the two alleles.
Article
Biochemistry & Molecular Biology
Ji Hoon Han, Gavin Ryan, Alyson Guy, Lu Liu, Mathieu Quinodoz, Ingrid Helbling, Joey E. Lai-Cheong, Julian Barwell, Marc Folcher, John A. McGrath, Celia Moss, Carlo Rivolta
Summary: The study identified LIPHAK as a previously unrecognized ribosomopathy, where variants in the LTV1 gene result in abnormal splicing and premature termination of the protein it encodes.
HUMAN MOLECULAR GENETICS
(2022)
Article
Oncology
Rafah Alnafakh, Gabriele Saretzki, Angela Midgley, James Flynn, Areege M. Kamal, Lucy Dobson, Purushothaman Natarajan, Helen Stringfellow, Pierre Martin-Hirsch, Shandya B. DeCruze, Sarah E. Coupland, Dharani K. Hapangama
Summary: The study found that dyskerin levels are significantly lower in endometrial cancer and are linked to the survival of women. Experimental results suggest that dyskerin may be a regulator of endometrial cancer cell proliferation, and may be a potential target for developing new therapies.
Article
Immunology
Benjamin Rolles, Andres Caballero-Oteyza, Michele Proietti, Sigune Goldacker, Klaus Warnatz, Nadezhda Camacho-Ordonez, Seraina Prader, Jana Pachlopnik Schmid, Margherita Vieri, Susanne Isfort, Robert Meyer, Martin Kirschner, Tim H. Bruemmendorf, Fabian Beier, Bodo Grimbacher
Summary: Telomere biology disorders (TBD) are genetic diseases caused by pathogenic variants in genes related to telomere maintenance. TBD can manifest in adulthood and have variable symptoms, making diagnosis complicated. Common variable immunodeficiency (CVID) is an antibody deficiency syndrome caused by dysfunctional B lymphocytes. In our study, we found that approximately 22% of CVID patients carried rare candidate variants in telomere-associated genes. We recommend including all TBD-associated genes in the genetic screening of patients with antibody deficiencies.
CLINICAL IMMUNOLOGY
(2023)
Review
Microbiology
Dominic P. Czekay, Ute Kothe
Summary: H/ACA sRNPs play crucial roles in ribosome synthesis in archaea and eukaryotes, with both shared general architecture and distinct differences in structure and function. Due to higher protein stability in archaea, there is more detailed information on archaeal H/ACA sRNPs compared to eukaryotes. Long-term studies in yeast have provided a better understanding of the biological role of H/ACA sRNPs in eukaryotes during ribosome biogenesis.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Hematology
Sally B. Killick, Nick Bown, Jamie Cavenagh, Inderjeet Dokal, Theodora Foukaneli, Anita Hill, Peter Hillmen, Robin Ireland, Austin Kulasekararaj, Ghulam Mufti, John A. Snowden, Sujith Samarasinghe, Anna Wood, Judith C. W. Marsh
BRITISH JOURNAL OF HAEMATOLOGY
(2016)
Letter
Hematology
Shirleny R. Cardoso, Alicia C. M. Ellison, Amanda J. Walne, David Cassiman, Manoj Raghavan, Bhuvan Kishore, Philip Ancliff, Carmen Rodriguez-Vigil, Bieke Dobbels, Ana Rio-Machin, Ahad F. H. Al Seraihi, Nikolas Pontikos, Hemanth Tummala, Tom Vulliamy, Inderjeet Dokal
Letter
Hematology
Shirleny R. Cardoso, Alicia C. M. Ellison, Amanda J. Walne, David Cassiman, Manoj Raghavan, Bhuvan Kishore, Philip Ancliff, Carmen Rodriguez-Vigil, Bieke Dobbels, Ana Rio-Machin, Ahad F. H. Al Seraihi, Nikolas Pontikos, Hemanth Tummala, Tom Vulliamy, Inderjeet Dokal
Letter
Hematology
Amanda Walne, Hemanth Tummala, Alicia Ellison, Shirleny Cardoso, Jasmin Sidhu, Gabriela Sciuccati, Tom Vulliamy, Inderjeet Dokal
Article
Oncology
Ahad F. Al Seraihi, Ana Rio-Machin, Kiran Tawana, Csaba Bodor, Jun Wang, Ai Nagano, James A. Heward, Sameena Iqbal, Steven Beset, Nicholas Lea, Donal McLornan, Emilia J. Kozyra, Marcin W. Wlodarski, Charlotte M. Niemeyer, Hamish Scott, Chris Hahn, Alicia Ellison, Hemanth Tummala, Shirleny Romualdo Cardoso, Tom Vulliamy, Inderjeet Dokal, Tom Butler, Matthew Smith, Jamie Cavenagh, Jude Fitzgibbon
Article
Multidisciplinary Sciences
Hemanth Tummala, Arran D. Dokal, Amanda Walne, Alicia Ellison, Shirleny Cardoso, Saranha Amirthasigamanipillai, Michael Kirwan, Isobel Browne, Jasmin K. Sidhu, Vinothini Rajeeve, Ana Rio-Machin, Ahad Al Seraihi, Andrew S. Duncombe, Matthew Jenner, Owen P. Smith, Helen Enright, Alice Norton, Tekin Aksu, Namik Yasar Ozbek, Nikolas Pontikos, Pedro Cutillas, Inderjeet Dokal, Tom Vulliamy
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Letter
Hematology
Amanda Walne, Hemanth Tummala, Alicia Ellison, Shirleny Cardoso, Jasmin Sidhu, Gabriela Sciuccati, Tom Vulliamy, Inderjeet Dokal
Letter
Hematology
Hemanth Tummala, Laura C. Collopy, Amanda J. Walne, Alicia Ellison, Shirleny Cardoso, Tekin Aksu, Nese Yarali, Deniz Aslan, Rustu Fikret Akata, Juliana Teo, Zhou Songyang, Nikolas Pontikos, Jude Fitzgibbon, Kazunori Tomita, Tom Vulliamy, Inderjeet Dokal
Article
Allergy
Markus G. Seidel, Gerhard Kindle, Benjamin Gathmann, Isabella Quinti, Matthew Buckland, Joris van Montfrans, Raphael Scheible, Stephan Ruschb, Lukas M. Gasteiger, Bodo Grimbacher, Nizar Mahlaoui, Stephan Ehl, Mario Abinun, Michael Albert, Sarah Beaussant Cohen, Jacinta Bustamante, Andrew Cant, Jean-Laurent Casanova, Helen Chapel, Genevieve de Saint Basile, Esther de Vries, Inderjeet Dokal, Jean Donadieu, Anne Durandy, David Edgar, Teresa Espanol, Amos Etzioni, Alain Fischer, Bobby Gaspar, Richard Gatti, Andrew Gennery, Sofia Grigoriadou, Steven Holland, Gritta Janka, Maria Kanariou, Christoph Klein, Helen Lachmann, Desa Lilic, Ania Manson, Natalia Martinez, Isabelle Meyts, Nicolette Moes, Despina Moshous, Benedicte Neven, Hans Ochs, Capucine Picard, Ellen Renner, Frederic Rieux-Laucat, Reinhard Seger, Annarosa Soresina, Dominique Stoppa-Lyonnet, Vojtech Thon, Adrian Thrasher, Frank van de Veer-Donk, Anna Villa, Corry Weemaes, Klaus Warnatz, Beata Wolska, Shen-Yin Zhang
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2019)
Article
Genetics & Heredity
Daphna Nachmani, Anne H. Bothmer, Silvia Grisendi, Aldo Mele, Dietmar Bothmer, Jonathan D. Lee, Emanuele Monteleone, Ke Cheng, Yang Zhang, Assaf C. Bester, Alison Guzzetti, Caitlin A. Mitchell, Lourdes M. Mendez, Olga Pozdnyakova, Paolo Sportoletti, Maria-Paola Martelli, Tom J. Vulliamy, Modi Safra, Schraga Schwartz, Lucio Luzzatto, Olivier Bluteau, Jean Soulier, Robert B. Darnell, Brunangelo Falini, Inderjeet Dokal, Keisuke Ito, John G. Clohessy, Pier Paolo Pandolfi
Article
Multidisciplinary Sciences
Ana Rio-Machin, Tom Vulliamy, Nele Hug, Amanda Walne, Kiran Tawana, Shirleny Cardoso, Alicia Ellison, Nikolas Pontikos, Jun Wang, Hemanth Tummala, Ahad Fahad H. Al Seraihi, Jenna Alnajar, Findlay Bewicke-Copley, Hannah Armes, Michael Barnett, Adrian Bloor, Csaba Bodor, David Bowen, Pierre Fenaux, Andrew Green, Andrew Hallahan, Henrik Hjorth-Hansen, Upal Hossain, Sally Killick, Sarah Lawson, Mark Layton, Alison M. Male, Judith Marsh, Priyanka Mehta, Rogier Mous, Josep F. Nomdedeu, Carolyn Owen, Jiri Pavlu, Elspeth M. Payne, Rachel E. Protheroe, Claude Preudhomme, Nuria Pujol-Moix, Aline Renneville, Nigel Russell, Anand Saggar, Gabriela Sciuccati, David Taussig, Cynthia L. Toze, Anne Uyttebroeck, Peter Vandenberghe, Brigitte Schlegelberger, Tim Ripperger, Doris Steinemann, John Wu, Joanne Mason, Paula Page, Susanna Akiki, Kim Reay, Jamie D. Cavenagh, Vincent Plagnol, Javier F. Caceres, Jude Fitzgibbon, Inderjeet Dokal
NATURE COMMUNICATIONS
(2020)
Article
Multidisciplinary Sciences
Hemanth Tummala, Amanda J. Walne, Findlay Bewicke-Copley, Alicia Ellison, Nikolas Pontikos, Maria G. Bridger, Ana Rio-Machin, Jasmin K. Sidhu, Jun Wang, Henrik Hasle, Jude Fitzgibbon, Tom Vulliamy, Inderjeet Dokal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Hematology
Amanda J. Walne, Tom Vulliamy, Findlay Bewicke-Copley, Jun Wang, Jenna Alnajar, Maria G. Bridger, Bernard Ma, Hemanth Tummala, Inderjeet Dokal
Summary: Gene expression profiling was performed on patients with inherited bone marrow failure (IBMF) subtypes, revealing common upregulation patterns in Fanconi anemia (FA), Shwachman-Diamond syndrome (SDS), and dyskeratosis congenita (DC) patients. Shared pathways in protein translation, RNA metabolism, and mitochondrial function were identified, along with a discovery set of 26 upregulated genes across IBMF subtypes. This study suggests a unified transcriptional drive in classic and uncharacterized IBMF subtypes, shedding light on disease pathogenesis and potential patient benefits.
Review
Hematology
Inderjeet Dokal, Hemanth Tummala, Tom Vulliamy
Summary: Inherited bone marrow failure syndromes are a group of diseases characterized by diverse manifestations and involvement of bone marrow failure. Significant progress has been made in the genetics of these diseases, revealing how genetic mutations disrupt normal hematopoiesis. Furthermore, these studies provide insights into human development and cancer. Genetic testing facilitates accurate diagnosis in clinical practice. Current treatment options have improved patient outcomes, but managing certain complications remains challenging.
Letter
Hematology
Sally B. Killick, Nick Bown, Jamie Cavenagh, Inderjeet Dokal, Theodora Foukaneli, Peter Hillmen, Robin Ireland, Austin Kulasekararaj, Ghulam Mufti, John A. Snowden, Sujith Samarasinghe, Anna Wood, Judith C. W. Marsh
BRITISH JOURNAL OF HAEMATOLOGY
(2018)
