Article
Orthopedics
Laurel A. Littrell, Carrie Y. Inwards, Florette K. Hazard, Doris E. Wenger
Summary: We report a case of a juvenile granulosa cell tumor (JGCT) in the ovarian tissue of a 15-year-old female patient. The patient presented with abnormal vaginal bleeding, several months of irregular menses, and a large multicystic adnexal mass. Imaging studies revealed multiple mixed lytic and sclerotic lesions in the bones of the pelvis, which were initially presumed to be skeletal metastases. However, biopsy tissue revealed a hyaline cartilage neoplasm. This case highlights the importance of recognizing the association between enchondromatosis and JGCT.
SKELETAL RADIOLOGY
(2023)
Article
Medicine, Research & Experimental
Qi Yang, Qiang Zhang, Fei Chen, Shang Yi, Mengting Li, Sheng Yi, Xingmin Xu, Jingsi Luo
Summary: The study identified compound novel heterozygous IFT122 variants in a male Chinese infant with Cranioectodermal dysplasia (CED), showing typical characteristics of CED as well as some unusual phenotypic features. The molecular confirmation of CED in this patient expands the associated variant spectrum of IFT122 in CED and provides additional clinical information regarding this syndrome. Additionally, the two identified variants in the proband offer a new perspective on the phenotypes caused by different combinations of variants.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Biotechnology & Applied Microbiology
Saba Abdi, Abeer Abdulaziz Almiman, Mohammed Ghouse Ahmed Ansari, Abdullah M. Alnaami, Abdul Khader Mohammed, Naji J. Aljohani, Amal Alenad, Amani Alghamdi, Majed S. Alokail, Nasser M. Al-Daghri
Summary: The study found that the PTHR1 rs1138518 genotype could be a potential risk factor for osteoporosis and regulation of 25-hydroxy-vitamin D in Arab women with postmenopausal osteoporosis.
BIOMED RESEARCH INTERNATIONAL
(2021)
Article
Cardiac & Cardiovascular Systems
Alexandros Protonotarios, Andreas Brodehl, Angeliki Asimaki, Joanna Jager, Ellie Quinn, Caroline Stanasiuk, Sandra Ratnavadivel, Marta Futema, Mohammed M. Akhtar, Thomas D. Gossios, Michael Ashworth, Konstantinos Savvatis, Volker Walhorn, Dario Anselmetti, Perry M. Elliott, Petros Syrris, Hendrik Milting, Luis R. Lopes
Summary: This study identified a DES variant in a large cohort of AC patients, leading to a disrupted desmin filament network and a biventricular form of AC characterized by myocardial fibrosis. The clinical phenotypes included heart transplantation, sudden death, and noncardiac death, with all cases showing right- and left-ventricular involvement and a circumferential subepicardial distribution of fibrosis.
CANADIAN JOURNAL OF CARDIOLOGY
(2021)
Article
Otorhinolaryngology
Kaitian Chen, Bixue Huang, Jincangjian Sun, Yue Liang, Guanxia Xiong
Summary: Children with congenital cochlear defects caused by CDH23 variants can achieve acceptable auditory and speech outcomes after cochlear implantation. Early genetic detection and prenatal counseling for rare deafness genes such as CDH23 remain a priority for the future.
OTOLARYNGOLOGY-HEAD AND NECK SURGERY
(2022)
Article
Clinical Neurology
Jie Wang, Jing-Da Qiao, Xiao-Rong Liu, De-Tian Liu, Yan-Hui Chen, Yi Wu, Yan Sun, Jing Yu, Rong-Na Ren, Zhen Mei, Yu-Xi Liu, Yi-Wu Shi, Mi Jiang, Si-Mei Lin, Na He, Bin Li, Wen-Jun Bian, Bing-Mei Li, Yong-Hong Yi, Tao Su, Han-Kui Liu, Wei-Yue Gu, Wei-Ping Liao
Summary: The study identified UNC13B gene variants in patients with partial epilepsy, suggesting a potential association with epilepsy, but patients with UNC13B variant-related epilepsy showed a favourable outcome under anti-epileptic therapy without intellectual or developmental abnormalities.
Article
Genetics & Heredity
Yasmin Soares de Lima, Coral Arnau-Collell, Jenifer Munoz, Cristina Herrera-Pariente, Leticia Moreira, Teresa Ocana, Marcos Diaz-Gay, Sebastia Franch-Exposito, Miriam Cuatrecasas, Sabela Carballal, Anael Lopez-Novo, Lorena Moreno, Guerau Fernandez, Aranzazu Diaz de Bustamante, Sophia Peters, Anna K. Sommer, Isabel Spier, Iris B. A. W. te Paske, Yasmijn J. van Herwaarden, Antoni Castells, Luis Bujanda, Gabriel Capella, Verena Steinke-Lange, Khalid Mahmood, JiHoon Eric Joo, Julie Arnold, Susan Parry, Finlay A. Macrae, Ingrid M. Winship, Christophe Rosty, Joaquin Cubiella, Daniel Rodriguez-Alcalde, Elke Holinski-Feder, Richarda de Voer, Daniel D. Buchanan, Stefan Aretz, Clara Ruiz-Ponte, Laura Valle, Francesc Balaguer, Laia Bonjoch, Sergi Castellvi-Bel
Summary: Rare germline variants in the WNK2 gene were identified through functional evaluation of a candidate gene and replication in additional SPS cohorts. These variants may affect protein function in the MAPK pathway, thereby increasing the risk for SPS.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Clinical Neurology
Charlotte Weinmann, Uwe Baumann, Martin Leinung, Timo Stoever, Silke Helbig
Summary: In this prospective study examining postoperative vertigo after cochlear implant, nearly half of the 29 adult participants experienced new dizziness symptoms. While subjective vertigo was suspected to be related to vestibular origin in the majority of cases, the study did not find significant correlations between subjective vertigo and various diagnostic tests performed.
FRONTIERS IN NEUROLOGY
(2021)
Article
Endocrinology & Metabolism
Wei Xuan Tan, Xueling Sim, Chin Meng Khoo, Adrian K. K. Teo
Summary: This Perspective article examines the tools and platforms that can be used to prioritize candidate genes associated with an increased risk of type 2 diabetes mellitus (T2DM) for functional validation. Despite the identification of numerous genetic variants associated with T2DM, translating these findings into potential drug targets has been limited. The article discusses the potential of different approaches, such as sequencing data with increased sample size and ethnic diversity, single-cell omics data, and glycaemic trait associations, to strengthen gene functionalization workflows and expedite our understanding of T2DM genetic mechanisms.
NATURE REVIEWS ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Julia M. Kempf, Sabrina Weser, Michael D. Bartoschek, Klaus H. Metzeler, Binje Vick, Tobias Herold, Kerstin Voelse, Raphael Mattes, Manuela Scholz, Lucas E. Wange, Moreno Festini, Enes Ugur, Maike Roas, Oliver Weigert, Sebastian Bultmann, Heinrich Leonhardt, Gunnar Schotta, Wolfgang Hiddemann, Irmela Jeremias, Karsten Spiekermann
Summary: Chemotherapy resistance in acute myeloid leukaemia is mainly hindered by loss-of-function mutations in EZH2, leading to upregulation of target genes providing selective growth advantage for cell survival and drug resistance.
SCIENTIFIC REPORTS
(2021)
Article
Clinical Neurology
Hiroshi Ikeda, Shigeru Yamaguchi, Yukitomo Ishi, Kento Wakabayashi, Ai Shimizu, Hiromi Kanno-Okada, Takeshi Endo, Mitsutoshi Ota, Michinari Okamoto, Hiroaki Motegi, Norimasa Iwasaki, Miki Fujimura
Summary: This article reports a case of a patient with Ollier disease who underwent surgery and was found to have multifocal tumors in the right and left frontal lobes. Pathological examinations revealed astrocytic tumor cells in the left frontal lobe tumor and IDH mutant and 1p/19q-codeleted oligodendroglioma in the right frontal lobe tumor. The study suggests that IDH1 R132H mutation is associated with the development of gliomas in the brain.
Article
Biotechnology & Applied Microbiology
Yun Tian, Qiong Liu, Yafang Zhou, Xiao-Yu Chen, Yongcheng Pan, Hongwei Xu, Zhuanyi Yang
Summary: A novel heterozygous missense mutation in EIF2B4 was found to be potentially associated with the adult-onset mild phenotype of VWM, and autosomal dominant inheritance was observed in adult-onset VWM for the first time.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Dermatology
A. Salava, V Salo, J. Leppanen, A. Lauerma, A. Remitz
Summary: This study investigated factors associated with severe atopic dermatitis in Finnish patients. The results showed that early onset, male sex, smoking history, overweight, concomitant asthma, palmar hyperlinearity, hand dermatitis, and high IgE levels were more frequent in severe cases of atopic dermatitis.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2022)
Article
Multidisciplinary Sciences
Kelly L. Bolton, Youngil Koh, Michael B. Foote, Hogune Im, Justin Jee, Choong Hyun Sun, Anton Safonov, Ryan Ptashkin, Joon Ho Moon, Ji Yeon Lee, Jongtak Jung, Chang Kyung Kang, Kyoung-Ho Song, Pyoeng Gyun Choe, Wan Beom Park, Hong Bin Kim, Myoung-don Oh, Han Song, Sugyeong Kim, Minal Patel, Andriy Derkach, Erika Gedvilaite, Kaitlyn A. Tkachuk, Brian J. Wiley, Ireaneus C. Chan, Lior Z. Braunstein, Teng Gao, Elli Papaemmanuil, N. Esther Babady, Melissa S. Pessin, Mini Kamboj, Luis A. Diaz, Marc Ladanyi, Michael J. Rauh, Pradeep Natarajan, Mitchell J. Machiela, Philip Awadalla, Vijai Joseph, Kenneth Offit, Larry Norton, Michael F. Berger, Ross L. Levine, Eu Suk Kim, Nam Joong Kim, Ahmet Zehir
Summary: Clonal hematopoiesis (CH) is associated with altered inflammatory profiles, increased risk of severe infections, particularly Covid-19, and other malignant diseases. Further investigation into the relationship between CH and severe infections may provide valuable insights for future research.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Jose Maria Garcia-Aznar, Emilia Maneiro Pampin, Maite Garcia Ramos, Maria Jose Acuna Perez, Nerea Paz Gandiaga, Laura Minguell Domingo, Olga Calavia, Pere Soler-Palacin, Roger Colobran, Erika M. Novoa Bolivar, Javier Gonzalo Ocejo Vinyals
Summary: We report five novel loss-of-function mutations in IRF2BP2 that likely cause primary immunodeficiency, with CVID as the most frequent phenotype, variable expression of inflammatory gastrointestinal features, and one patient with predisposition to viral infection. These mutations include frameshift changes and a large deletion on chromosome 1q42, which includes the whole sequence of IRF2BP2. Both de novo and dominant modes of inheritance were observed, as well as incomplete penetrance.
FRONTIERS IN IMMUNOLOGY
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Alexandre Persu, Miikka Vikkula, Bart Loeys
CARDIOVASCULAR RESEARCH
(2021)
Review
Genetics & Heredity
Richard Coulie, Dmitriy M. Niyazov, Michael J. Gambello, Elodie Fastre, Pascal Brouillard, Miikka Vikkula
Summary: HLTS is a rare condition caused by pathogenic variants in the SOX18 gene, with main symptoms including sparse hair, lymphedema, and telangiectatic lesions; only a few patients have additional features such as renal failure, arterial or pulmonary hypertension, and aortic dilatation; a new case of HLTS with a 14-nucleotide de novo duplication in SOX18 and congenital ileal atresia has been reported.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Review
Cardiac & Cardiovascular Systems
Taija Makinen, Laurence M. Boon, Miikka Vikkula, Kari Alitalo
Summary: Lymphatic vessels play a crucial role in maintaining tissue fluid homeostasis and immune surveillance. Developmental or functional defects in lymphatic vessels can lead to lymphedema. Recent advancements have identified genetic causes and molecular pathways underlying lymphatic malformations and complex lymphatic anomalies, paving the way for targeted therapies.
CIRCULATION RESEARCH
(2021)
Review
Cardiac & Cardiovascular Systems
Angela Queisser, Emmanuel Seront, Laurence M. Boon, Miikka Vikkula
Summary: In recent years, research on genetic and somatic mutations in vascular and lymphatic malformations has led to the evaluation of preexisting cancer drugs that interfere with these signaling pathways, marking the beginning of personalized treatment for vascular anomalies.
CIRCULATION RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Alain Couvineau, Pascal Nicole, Valerie Gratio, Thierry Voisin
Summary: Orexin neuropeptides and their receptors play crucial roles in wakefulness, food consumption, hormone secretion, and blood pressure regulation. The expression of OX1R in various cancers may have a therapeutic potential by inducing apoptosis in tumor cells.
Article
Medicine, Research & Experimental
Nassim Homayun-Sepehr, Anna L. McCarter, Raphael Helaers, Christine Galant, Laurence M. Boon, Pascal Brouillard, Miikka Vikkula, Michael T. Dellinger
Summary: Gorham-Stout disease (GSD) is a rare lymphatic disorder with severe complications whose etiology is still unclear. Research shows that somatic activating mutations in the KRAS gene may be associated with GSD, and hyperactive KRAS signaling stimulates the formation of lymphatics in bone.
Article
Genetics & Heredity
Marie F. Smeland, Pascal Brouillard, Trine Prescott, Laurence M. Boon, Bodil Hvingel, Cecilie Nordbakken, Mona Nystad, Oystein L. Holla, Miikka Vikkula
Summary: This study investigated a consanguineous family with recurrent pregnancy loss due to severe early-onset non-immune hydrops fetalis. The researchers found that the fetuses had a homozygous pathogenic variant in the ANGPT2 gene, leading to loss-of-function. This is the first report of an autosomal recessive ANGPT2-related disorder in humans.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Gastroenterology & Hepatology
Alain Couvineau, Thierry Voisin, Pascal Nicole, Valerie Gratio, Anne Blais
Summary: Hypothalamic neuropeptides hypocretin/orexins, identified in 1998, not only regulate important functions in the central nervous system but also play a role in the peripheral nervous system. Their involvement in various physiological functions and diseases such as inflammation, metabolic syndrome, and cancers suggests that they could be potential therapeutic targets for multiple pathologies.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Medicine, General & Internal
Pascal Brouillard, Marlys H. Witte, Robert P. Erickson, Robert J. Damstra, Corinne Becker, Isabelle Quere, Miikka Vikkula
Summary: Lymphoedema is the swelling caused by lymph accumulation in the extracellular space, often chronic and resulting in reduced quality of life if untreated. Primary lymphoedema (PLE) is believed to have a genetic origin, with mutations in genes affecting lymphatic system development; diagnosis relies on clinical presentation, imaging, and genetic analyses, while management includes compression therapy and surgical techniques. Improved understanding of the genetic origins of PLE will lead to more accurate diagnosis and personalized treatment options for affected individuals.
NATURE REVIEWS DISEASE PRIMERS
(2021)
Article
Biochemistry & Molecular Biology
Ingrid Langer, Jerome Jeandriens, Alain Couvineau, Swapnil Sanmukh, Dorota Latek
Summary: This article discusses the regulation of human immune system homeostasis by neuropeptides such as VIP and PACAP, as well as their interactions with receptors VPAC1, VPAC2, and PAC1. It also introduces the new concept of inhibiting VIP and PACAP receptors for the treatment of chronic inflammation and cancer, and the neuroprotective effects of activating these receptors.
Review
Dentistry, Oral Surgery & Medicine
Julien Coulie, Laurence Boon, Miikka Vikkula
Summary: Vascular anomalies are a heterogeneous group of vascular lesions that can be divided into vascular tumors and vascular malformations. Correct diagnosis is crucial for selecting the best treatment, which traditionally includes surgery, embolization, or sclerotherapy. Medical treatment has become increasingly important in the management of vascular anomalies. Understanding the molecular causes and involved pathways allows for the use of targeted medical therapies.
JOURNAL OF ORAL PATHOLOGY & MEDICINE
(2022)
Review
Genetics & Heredity
Matheus de Mello Copelli, Eleonore Pairet, Milena Atique-Tacla, Tarsis Paiva Vieira, Simone Appenzeller, Raphael Helaers, Miikka Vikkula, Vera Lucia Gil-da-Silva-Lopes
Summary: SATB2-associated syndrome (SAS) is a rare genetic condition characterized by severe developmental delay/intellectual disability, especially in speech, craniofacial abnormalities, and behavioral problems. This case study of a 25-year-old male with SAS contributes to the understanding of the natural history of the disease and highlights the management challenges associated with the SATB2:c.715C>T:p.(Arg239*) variant.
Article
Biochemistry & Molecular Biology
Milena Atique Tacla, Matheus de Mello Copelli, Eleonore Pairet, Isabella Lopes Monlleo, Erlane Marques Ribeiro, Elaine Lustosa Mendes, Raphael Helaers, Tarsis Paiva Vieira, Miikka Vikkula, Vera Lucia Gil-da-Silva-Lopes
Summary: This study presents genomic findings among individuals with both orofacial clefts and microphthalmia/anophthalmia/coloboma, and highlights the effectiveness of Whole Exome Sequencing (WES) in diagnosing this condition. The study also emphasizes the importance of genes associated with ciliopathies in this phenotype.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Anne Blais, Annaig Lan, Francois Blachier, Robert Benamouzig, Pauline Jouet, Alain Couvineau
Summary: Inflammatory bowel diseases are chronic inflammation characterized by relapsing-remitting cycles. The study aimed to compare the efficacy of IFX and OxA in a mouse model of chemically induced colitis. OxA treatment demonstrated better efficiency in promoting mucosal healing and suppressing inflammatory factors compared to IFX, suggesting its potential as a promising new biotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Simon Boutry, Raphael Helaers, Tom Lenaerts, Miikka Vikkula
Summary: The development of high-throughput next-generation sequencing technologies and large-scale genetic association studies has led to advances in the field of biostatistics. This study proposes a new ensemble method called Excalibur, which combines 36 aggregation tests to provide the best aggregation analysis for genetic regions of interest. The results demonstrate the ability of Excalibur to control type I error and offer the highest average power across all scenarios.
PLOS COMPUTATIONAL BIOLOGY
(2023)