Editorial Material
Rheumatology
Sarah Onuora
Summary: New research has identified an autoinflammatory syndrome caused by mutations in NEMO-encoding IKBKG, leading to activation of NF-kappa B and production of type I interferon.
NATURE REVIEWS RHEUMATOLOGY
(2022)
Article
Cell Biology
Annibale Alessandro Puca, Valentina Lopardo, Francesco Montella, Paola Di Pietro, Daniela Cesselli, Irene Giulia Rolle, Michela Bulfoni, Veronica Di Sarno, Giorgio Iaconetta, Pietro Campiglia, Carmine Vecchione, Antonio Paolo Beltrami, Elena Ciaglia
Summary: Glioblastoma is the most common primary brain cancer, with aging being an important risk factor. Current anti-GBM therapies induce cellular senescence and the release of proinflammatory SASP factors, highlighting the need for adjuvant therapies that limit cellular senescence.
Article
Multidisciplinary Sciences
Zeinab Klaab, Abeer Al Tuwaijri, Muhammad Umair, Badr Aldahmash, Majid Alfadhel
Summary: This study identified a novel homozygous splice site variant in the CLCN7 gene as the cause of severe autosomal recessive osteopetrosis in two consanguineous Saudi families. The findings highlight the importance of this gene in the pathogenesis of osteopetrosis and its implications for clinical therapeutic regimens, prognosis assessment, and antenatal diagnosis.
JOURNAL OF KING SAUD UNIVERSITY SCIENCE
(2023)
Article
Dermatology
Xing Xiong, Syed Ashraf Uddin, Sobia Munir, Nicole Cesarato, Holger Thiele, Noor Hassan, Surjeet Kumar, Fazal Ur Rehman, Muhammad Naeem, Abdul Wali, Sulman Basit, F. Buket Basmanav, Muhammad Ayub, Regina C. Betz
Summary: A novel homozygous disease-causing variant in TMC8 was identified in a Pakistani family with epidermodysplasia verruciformis (EV). The phenotype of EV in the affected individuals was most likely caused by aberrant splicing process. The molecular genetic findings in this study expand the mutational spectrum of the disease.
CLINICAL AND EXPERIMENTAL DERMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Stephen J. Pettitt, Nan Shao, Diana Zatreanu, Jessica Frankum, Ilirjana Bajrami, Rachel Brough, Dragomir B. Krastev, Theodoros I. Roumeliotis, Jyoti S. Choudhary, Sonja Lorenz, Alistair Rust, Johann S. de Bono, Timothy A. Yap, Andrew N. J. Tutt, Christopher J. Lord
Summary: Reduced expression of HUWE1 leads to increased levels of BRCA1- increment 11q and PARPi resistance. This effect is specific to cells able to express BRCA1- increment 11q and is not seen in other BRCA1 or BRCA2 mutant cells. HUWE1 silencing also restores RAD51 nuclear foci and platinum salt resistance, indicating its potential as a biomarker for PARPi resistance in future clinical trials.
Article
Hematology
Makoto Osada, Keiko Maruyama, Koichi Kokame, Ryunosuke Denda, Kohei Yamazaki, Hisako Kunieda, Maki Hirao, Seiji Madoiwa, Nobuo Okumura, Mitsuru Murata, Yasuo Ikeda, Kentaro Watanabe, Yuiko Tsukada, Takahide Kikuchi
Summary: A 19-year-old Vietnamese woman experienced life-threatening bleeding events, which were not corrected by hemostatic surgery and medications, but remarkably improved with recombinant human thrombomodulin. A novel homozygous variation in the TM gene was identified through screening and sequencing, possibly leading to reduced TM expression on endothelial cell membrane. This reduced expression may explain the disseminated intravascular-coagulation-like symptoms observed in the patient.
Article
Genetics & Heredity
Nimrod Sachs, Oded Wechsberg, Yuval E. Landau, Irit Krause, Ifat Israel Elgali, Malak Darawshe, Noam Shomron, Gabriel Lidzbarsky, Naama Orenstein
Summary: Citrin deficiency is an autosomal recessive disorder caused by pathogenic variants in the SLC25A13 gene. It presents in neonates as failure to thrive and acute liver insufficiency. A case of Citrin deficiency in a 4-week-old infant was diagnosed through comprehensive biochemical and molecular analysis, revealing a previously unknown damaging variant of the SLC25A13 gene.
Article
Multidisciplinary Sciences
Ines Sturmlechner, Chance C. Sine, Karthik B. Jeganathan, Cheng Zhang, Raul O. Fierro Velasco, Darren J. Baker, Hu Li, Jan M. van Deursen
Summary: Super-enhancers regulate genes that are important for specific cell functions or defining cell identity. Senescent cells have survival mechanisms that involve inhibiting p53-mediated apoptosis through multiple mechanisms, including binding to ribonucleases.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Yi-Dan Liu, Dan-Dan Tan, Dan-Yu Song, Yan-Bin Fan, Xiao-Na Fu, Lin Ge, Wei Wei, Hui Xiong
Summary: This study reports a case of muscle-eye-brain disease (MEB) caused by a homozygous variant of the POMGNT1 gene, which was identified through uniparental disomy (UPD). Genetic testing revealed a c.636C>T variant in exon 7 of POMGNT1 in the patient, as well as in the father, while the mother had the wild type. Further analysis showed paternal UPD on chromosome 1 in the patient.
FRONTIERS IN GENETICS
(2023)
Article
Clinical Neurology
Pooja Pravinbabu, Vikram V. Holla, Prashant Phulpagar, Nitish Kamble, Manjunath Netravathi, Ravi Yadav, Pramod Kumar Pal, Babylakshmi Muthusamy
Summary: This study describes the clinical and genetic features of a 17-year-old male with CMT4D, identifying a novel deletion mutation in the NDRG1 gene. The study expands the understanding of the clinical and genetic spectrum of CMT4D and suggests a novel splice isoform of NDRG1 as a potential cause for the neuropathy observed in this patient.
NEUROLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Lein N. H. Dofash, Gavin Monahan, Emilia Servian-Morilla, Eloy Rivas, Fathimath Faiz, Patricia Sullivan, Emily Oates, Joshua Clayton, Rhonda L. Taylor, Mark R. Davis, Traude Beilharz, Nigel G. Laing, Macarena Cabrera-Serrano, Gianina Ravenscroft
Summary: Nemaline myopathy 8 (NEM8) is a severe autosomal recessive disorder caused by variants in the KLHL40 gene. This study reports a case of a 26-year-old man with mild NEM8, characterized by hypotonia, fractures, and contractures. Genetic analysis identified compound heterozygous variants in KLHL40, including a truncating deletion and a likely pathogenic variant in the 3' UTR. Functional analysis revealed that the 3' UTR variant induced aberrant splicing and decreased expression of KLHL40 mRNA and protein. This study highlights the importance of considering abnormal 3' UTR splicing in variant curation for Mendelian diseases.
HUMAN MOLECULAR GENETICS
(2023)
Article
Immunology
Manfred Fliegauf, Renate Krueger, Sophie Steiner, Leif Gunnar Hanitsch, Sarah Buechel, Volker Wahn, Horst von Bernuth, Bodo Grimbacher
Summary: In a German family, a previously uncharacterized heterozygous NFKB1 missense variant was identified in four members diagnosed with common variable immunodeficiency (CVID). The clinical phenotypes varied among affected family members but supported a disease mechanism provoked by a p105/p50 (haplo)insufficient condition in the presence of the pathogenic NFKB1 variant.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Agriculture, Dairy & Animal Science
Paulina G. Eusebi, Oscar Cortes, Elisabeth Contreras, Javier Canon, Susana Dunner, Natalia Sevane
Summary: This study conducted an association study and whole genome re-sequencing analysis on the growth and respiratory lethal syndrome in the Spanish Lidia cattle breed. A novel missense variant in the EDN2 gene was identified, which is predicted to have damaging effects on the structure and function of the edn2 protein. This discovery enables efficient mating design and provides insights into the first EDN2-associated hereditary disease in cattle or other species.
Article
Genetics & Heredity
Shridhar Parthasarathy, Sarah McKeown Ruggiero, Antoinette Gelot, Fernanda C. Soardi, Bethania F. R. Ribeiro, Douglas E. Pires, David B. Ascher, Alain Schmitt, Caroline Rambaud, Alfonso Represa, Hongbo M. Xie, Laina Lusk, Olivia Wilmarth, Pamela Pojomovsky McDonnell, Olivia A. Juarez, Alexandra N. Grace, Julien Buratti, Cyril Mignot, Domitille Gras, Caroline Nava, Samuel R. Pierce, Boris Keren, Benjamin C. Kennedy, Sergio D. J. Pena, Ingo Helbig, Vishnu Anand Cuddapah
Summary: Pathogenic variants affecting exon 10a of the DNM1 gene have been found to cause severe developmental and epileptic encephalopathy. This study highlights the importance of considering gene isoforms and the mechanism of splice site variants in disease research.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Genetics & Heredity
Lin Zhang, Wenwu Li, Yuting Weng, Keqin Lin, Kai Huang, Shaohui Ma, Jiayou Chu, Zhaoqing Yang, Xiaochao Zhang, Hao Sun
Summary: Limb-Girdle muscular dystrophy (LGMD) is a group of muscle disorders with highly heterogeneous genetic patterns and clinical phenotypes. Accurate diagnosis of different LGMD subtypes requires a combination of clinical analysis and genetic testing. This study identified a novel homozygous POPDC3 variant associated with a specific LGMD subtype, expanding the gene variant spectrum of POPDC3.