Review
Cardiac & Cardiovascular Systems
Pishoy Gouda, Robert Kay, Marina Habib, Amir Aziz, Eitan Aziza, Robert Welsh
Summary: Loeys-Dietz syndrome (LDS) is a multisystem connective tissue disorder caused by mutations in the transforming growth factor 1 signalling pathway. It is characterized by features such as aortic aneurysms and dissections, arterial tortuosity, and high arched palate. Different types of LDS have varying clinical features and complications, with LDS Type 2 being associated with more severe aortic disease.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2022)
Article
Genetics & Heredity
Stefano Nistri, Rosina De Cario, Elena Sticchi, Gaia Spaziani, Matteo Della Monica, Sabrina Giglio, Silvia Favilli, Betti Giusti, Pierluigi Stefano, Guglielmina Pepe
Summary: Marfan syndrome (MFS) and Loeys-Dietz syndrome type 4 (LDS4) are two hereditary connective tissue disorders with overlapping clinical manifestations but different characteristics, and age plays a role in the onset of symptoms.
Article
Cardiac & Cardiovascular Systems
Peter Ewert, Frank Harig
Summary: The aim of the study was to explore the relationship between aortic size and body composition in Marfan syndrome and Loeys-Dietz syndrome patients. The results revealed that many patients did not fit the expected slender phenotype and were obese, which was associated with a more severe aortic phenotype.
CARDIOVASCULAR DIAGNOSIS AND THERAPY
(2022)
Article
Genetics & Heredity
Daniel Maghsoudi, Thomas R. W. Nixon, Martin P. Snead
Summary: Loeys-Dietz syndrome is a connective tissue disorder similar to Marfan syndrome, but retinal detachment is rarely reported. This study reports a 5-generation family affected by LDS, where 6 eyes of 4 individuals had retinal detachment. The study suggests that ophthalmic examination should be added to the initial assessment of LDS patients and patients should be informed of the early warning symptoms of retinal detachment.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Biochemistry & Molecular Biology
Paola Fortugno, Rosanna Monetta, Valeria Cinquina, Chiara Rigon, Francesca Boaretto, Chiara De Luca, Nicoletta Zoppi, Luana Di Leandro, Emanuela De Domenico, Arianna Di Daniele, Rodolfo Ippoliti, Francesco Angelucci, Ernesto Di Cesare, Ruggero De Paulis, Leonardo Salviati, Marina Colombi, Francesco Brancati, Marco Ritelli
Summary: Pathogenic variants in TGFBR1 are a common cause of Loeys-Dietz syndrome (LDS) characterized by life-threatening cardiovascular diseases. In this study, two novel variants in TGFBR1 were identified in LDS patients, resulting in truncated TGFBR1 proteins. These variants escaped nonsense-mediated mRNA decay and exhibited enhanced TGF beta signaling. The findings emphasize the importance of functional studies for accurate clinical diagnosis.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Ophthalmology
Wenting Wang, Hui Man, Jie Zhang, Penglin Yu, Shuchan Li, Xinyan Xu, Nan Li
Summary: Ocular findings in LDS patients, particularly the fundus, are rarely reported, but should be carefully examined to identify potential issues.
EUROPEAN JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Yoshimasa Seike, Hitoshi Matsuda, Hatsue Ishibashi-Ueda, Hiroko Morisaki, Takayuki Morisaki, Kenji Minatoya, Hitoshi Ogino
Summary: This study identified differences in surgical outcomes between LDS patients with TGFBR1 and TGFBR2 mutations. Patients with TGFBR2 mutations had higher grade of CMN, with a higher frequency of AD and reoperation after the initial surgery, particularly in female patients.
ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY
(2021)
Article
Cardiac & Cardiovascular Systems
Przemyslaw Chmielewski, Joanna K. Poninska, Ewa Michalak, Ilona Michalowska, Ilona Kowalik, Grazyna Truszkowska, Monika Kugaudo, Ilona Minota, Piotr Stawinski, Rafal Ploski, Zofia T. Bilinska
Summary: Loeys-Dietz syndrome (LDS) is an inherited connective tissue disorder associated with aortic complications, commonly occurring in young individuals. This study analyzed clinical data of LDS patients and observed a high prevalence of cardiovascular complications.
KARDIOLOGIA POLSKA
(2023)
Article
Genetics & Heredity
Deanna Fry, Daniel Groepper, Gretchen MacCarrick, Erin M. Demo, Matthew J. Thomas, Margaret J. Wilkes, Michael J. Lyons, Megan E. Tucker, Catherine Steding, Julie Fleischer
Summary: Loeys-Dietz syndrome (LDS) is a connective tissue disorder that often leads to cardiovascular issues such as a dilated aorta, congenital heart defects, joint laxity, and others. A recent report found that patients with LDS had a deletion in a 785kb region on their chromosome, which includes the RRP15 and TGFB2 genes.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Obstetrics & Gynecology
Yang Yang, Wang Yan, Mao Aifen, Wang Hao
Summary: This article presents a rare atypical case of Loeys-Dietz syndrome 1 in a prenatal setting, reporting a novel mutation in the TGFBR1 gene. Trio-based whole exome sequencing was used for diagnosis, revealing that the fetus did not demonstrate the characteristic phenotype of the syndrome. The study highlights the challenges in prenatal fetal phenotyping and emphasizes the importance of molecular techniques.
TAIWANESE JOURNAL OF OBSTETRICS & GYNECOLOGY
(2022)
Article
Genetics & Heredity
Lois Janelle Starr, Mark Evan Lindsay, Christian Lino Cardenas, Anji T. Yetman
Summary: This study reports a case of siblings with a biallelic type of TGFBR1-related disease, characterized by severe health issues including aortic root dilation, congenital diaphragmatic hernia, skin translucency, and joint laxity. It is revealed that the disease is associated with compound heterozygous variants in the TGFBR1 gene.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Review
Pediatrics
Francesco Baldo, Laura Morra, Agnese Feresin, Flavio Faletra, Yasmin Al Naber, Luigi Memo, Laura Travan
Summary: Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder characterized by cardiovascular manifestations, craniofacial and skeletal features, and other abnormalities. Early diagnosis is crucial in preventing complications. Case reports and literature review suggest that early intervention can modify the natural history of the disease, highlighting the multiple benefits of early diagnosis.
ITALIAN JOURNAL OF PEDIATRICS
(2022)
Letter
Genetics & Heredity
Toshiaki Asano, Kazuma Oku, Hiroyuki Kondo
Summary: This study presented a case of a 15-year-old boy diagnosed with FEVR with a heterozygous deletion mutation in the TGFBR2 gene identified through whole exome sequencing. The presence of a de novo mutation in the absence of systemic abnormalities associated with LDS suggests that FEVR can be linked to TGFBR2 mutations independently of LDS.
OPHTHALMIC GENETICS
(2021)
Article
Genetics & Heredity
Melanie H. A. M. Perik, Emmanuela Govaerts, Steven Laga, Inge Goovaerts, Johan Saenen, Emeline Van Craenenbroeck, Josephina A. N. Meester, Ilse Luyckx, Inez Rodrigus, Aline Verstraeten, Lut Van Laer, Bart L. Loeys
Summary: This study provides insights into the clinical features of individuals with TGFB3 variants causing Loeys-Dietz syndrome type 5, specifically focusing on individuals from the Campine region in Flanders. The study reveals a shared haplotype among individuals from different families, suggesting a common founder more than 400 years ago. Despite the variants, the penetrance of aortic aneurysm/dissection is low, indicating the involvement of additional factors in the development of the aneurysm phenotype.
FRONTIERS IN GENETICS
(2023)
Article
Ophthalmology
Yao Lu, Zhizhong Ma
Summary: This case report describes a unique retinal finding in a patient with Loeys-Dietz syndrome. The patient, a 30-year-old female with LDS, was found to have retinal arterial macroaneurism (RAM) in the left eye. Treatment with laser photocoagulation and transscleral diode photocoagulation successfully resolved the subretinal fluid. The finding of RAM is related to a novel mutation of TGFBR1 gene in LDS.
EUROPEAN JOURNAL OF OPHTHALMOLOGY
(2023)
Editorial Material
Immunology
Joe Davis Velchev, Aline Verstraeten, Bart Loeys
JOURNAL OF EXPERIMENTAL MEDICINE
(2020)
Review
Biochemistry & Molecular Biology
Aleksandra Nijak, Johan Saenen, Alain J. Labro, Dorien Schepers, Bart L. Loeys, Maaike Alaerts
Summary: Brugada syndrome is an inherited cardiac arrhythmia that can lead to ventricular fibrillation and sudden cardiac death. The use of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offers new opportunities for studying complex cardiac arrhythmia syndromes. iPSC-CMs are considered the best in vitro model for researching Brugada syndrome and other arrhythmias.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Ilse Van Gucht, Josephina A. N. Meester, Jotte Rodrigues Bento, Maaike Bastiaansen, Jarl Bastianen, Ilse Luyckx, Lotte Van den Heuvel, Cedric H. G. Neutel, Pieter-Jan Guns, Mandy Vermont, Erik Fransen, Melanie H. A. M. Perik, Joe Davis Velchev, Maaike Alaerts, Dorien Schepers, Silke Peeters, Isabel Pintelon, Abdulrahman Almesned, Matteo P. Ferla, Jenny C. Taylor, Anthony R. Dallosso, Maggie Williams, Julie Evans, Jill A. Rosenfeld, Thierry Sluysmans, Desiderio Rodrigues, Ashish Chikermane, Gangadhara Bharmappanavara, Kayal Vijayakumar, Hassan Mottaghi Moghaddam Shahri, Narges Hashemi, Paria Najarzadeh Torbati, Mehran B. Toosi, Zuhair N. Al-Hassnan, Julie Vogt, Nicole Revencu, Isabelle Maystadt, Erin M. Miller, K. Nicole Weaver, Amber Begtrup, Henry Houlden, David Murphy, Reza Maroofian, Alistair T. Pagnamenta, Lut Van Laer, Bart L. Loeys, Aline Verstraeten
Summary: Importin 8, encoded by IPO8, is crucial for the development of thoracic aortic aneurysm (TAA) and its loss-of-function variants may cause a syndromic form of TAA with clinical overlap with other syndromes. Importin 8 plays a role in dysregulation of the TGF-beta signaling pathway, providing potential for future mechanistic studies and drug targeting in TAA.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Review
Cardiac & Cardiovascular Systems
Lucia Mazzolai, Adriano Alatri, Alessandra Bura Riviere, Marco De Carlo, Christian Heiss, Christine Espinola-Klein, Oliver Schlager, Henrik Sillesen, Daniel Staub, Jose F. Rodriguez-Palomares, Aline Verstraeten, Victor Aboyans
Summary: This review article summarizes key research on vascular diseases published in 2020, including studies on aortic aneurysm, fibromuscular dysplasia (FMD), the role of NADPH oxidases in vascular physiology, imaging of vulnerable plaque, and clinical trials on lower extremity peripheral artery disease.
CARDIOVASCULAR RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Ilse Van Gucht, Alice Krebsova, Birgitte Rode Diness, Steven Laga, Dave Adlam, Marlies Kempers, Nilesh J. Samani, Tom R. Webb, Ania A. Baranowska, Lotte van den Heuvel, Melanie Perik, Ilse Luyckx, Nils Peeters, Pavel Votypka, Milan Macek, Josephina Meester, Lut Van Laer, Aline Verstraeten, Bart L. Loeys
Summary: This study found that patients with LOX gene variants have a spectrum of aortic and arterial aneurysmal diseases, often combined with connective tissue abnormalities. Some patients developed TAAD in early life, while others had normal aortic diameters in advanced age.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Jotte Rodrigues Bento, Candice Feben, Marlies Kempers, Maartje Rij, Mallory Woiski, Koenraad Devriendt, Luc De Catte, Marcella Baldewijns, Maaike Alaerts, Josephina Meester, Aline Verstraeten, Willy Hendson, Bart Loeys
Summary: The study identifies pathogenic mutations in KCNMA1 gene associated with a wide range of clinical manifestations, including aortic dilatation, growth retardation, and neurological dysfunction. The p.Gly375Arg variant is linked to aortic root dilatation, gingival hypertrophy, and neonatal overgrowth, while the p.Pro805Leu variant is associated with severe neurological manifestations.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Medicine, Research & Experimental
Annemieke Smet, Tom Breugelmans, Johan Michiels, Kevin Lamote, Wout Arras, Joris G. De Man, Leo Heyndrickx, Anne Hauner, Manon Huizing, Surbhi Malhotra-Kumar, Martin Lammens, An Hotterbeekx, Samir Kumar-Singh, Aline Verstraeten, Bart Loeys, Veronique Verhoeven, Rita Jacobs, Karolie Dams, Samuel Coenen, Kevin K. Arien, Philippe G. Jorens, Benedicte Y. De Winter
Summary: By analyzing the expression profiles of mucins in COVID-19 patients, it is possible to improve diagnosis, assess disease severity, and guide treatment options. The mucin mRNA signature can accurately differentiate the severity of the disease among patients and is associated with clinical parameters such as symptoms and organ failure.
Review
Genetics & Heredity
Silke Peeters, Pauline De Kinderen, Josephina A. N. Meester, Aline Verstraeten, Bart L. Loeys
Summary: This article explores the phenotypic and molecular similarities between Marfan syndrome and acromelic dysplasias caused by pathogenic variants in the FBN1 and FBN2 genes. The parallel functional study of these disorders may provide insights into the effects of fibrillin variants on the microfibril network and growth factor homeostasis, leading to the development of new therapeutic approaches.
Article
Cardiac & Cardiovascular Systems
Hanne M. Boen, Bart L. Loeys, Maaike Alaerts, Johan B. Saenen, Inge Goovaerts, Lut Van Laer, Anne Vorlat, Tom Vermeulen, Constantijn Franssen, Patrick Pauwels, Inez Rodrigus, Hein Heidbuchel, Emeline M. Van Craenenbroeck
Summary: The study investigates the yield and importance of genetic testing in heart transplant patients with non-ischemic cardiomyopathy. The results show that genetic testing in these patients can establish a molecular diagnosis and is recommended for identifying at-risk relatives, regardless of family history or second precipitating factors.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2022)
Article
Cell & Tissue Engineering
Joe Davis Velchev, Aline Verstraeten, Josephina Meester, Peter Ponsaerts, Julie Richer, Maaike Alaerts, Bart Loeys
Summary: This study generated an induced pluripotent stem cell line from a severely affected Loeys-Dietz Syndrome patient and demonstrated its pluripotency, providing a valuable tool for studying and targeting the cellular mechanisms of SMAD3-related LDS.
STEM CELL RESEARCH
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Aline Verstraeten, Ivanna Fedoryshchenko, Bart Loeys
EUROPEAN HEART JOURNAL
(2023)
Review
Genetics & Heredity
Ilse Luyckx, Aline Verstraeten, Marie-Jose Goumans, Bart Loeys
Summary: This article reviews the clinical and genetic similarities of three diseases related to SMAD6, compares mouse models, and discusses the cellular mechanisms of SMAD6 in the development of these diseases. The importance of further research to improve molecular diagnosis, advance therapeutic strategies, and provide counseling for patients and their families is also emphasized.
NPJ GENOMIC MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Eline Simons, Bart Loeys, Maaike Alaerts
Summary: The discovery of induced pluripotent stem cells has allowed the generation of various cell types, including iPSC-derived cardiomyocytes, for different purposes such as disease modelling and drug discovery. While 2D iPSC-CM models have shown promise, they are less mature compared to adult cardiomyocytes. Novel approaches are being developed to create 3D models with added cell types, improving maturity and physiological relevance. This review focuses on the progress in modelling inherited cardiac arrhythmias using both 2D and 3D models, and their application in therapy development and drug testing.
Article
Cell & Tissue Engineering
Lotte J. F. Van Den Heuvel, Silke Peeters, Josephina A. N. Meester, Melanie Perik, Paul Coucke, Bart L. Loeys
Summary: Marfan syndrome is a connective tissue disorder characterized by manifestations in the ocular, skeletal, and cardiovascular system, often caused by pathogenic variants in the FBN1 gene. We have generated an induced pluripotent cell (iPSC) line from a Marfan syndrome patient with an FBN1 c.7754T > C (p. Ile2585Thr) variant. The iPSC line derived from peripheral blood mononuclear cells showed no copy number alterations, expressed pluripotency markers, and could differentiate into three germ layers while maintaining the original genotype.
STEM CELL RESEARCH
(2023)
Article
Cell & Tissue Engineering
Silke Peeters, Ivanna Fedoryshchenko, Laura Rabaut, Aline Verstraeten, Bart L. Loeys
Summary: Marfan syndrome (MFS) is a connective tissue disorder that affects the ocular, skeletal, and cardiovascular systems. It is caused by pathogenic variants in the FBN1 gene. This study successfully generated an induced pluripotent cell (iPSC) line from a MFS patient carrying a FBN1 c.5372G > A (p.Cys1791Tyr) variant. The iPSCs exhibited normal characteristics and maintained the original genotype.
STEM CELL RESEARCH
(2023)
