Article
Critical Care Medicine
Davide Elia, Olga Torre, Chiara Vasco, Jens Geginat, Sergio Abrignani, Elisabetta Bulgheroni, Elena Carelli, Roberto Cassandro, Gustavo Pacheco-Rodriguez, Wendy K. Steagall, Joel Moss, Sergio Harari
Summary: This study investigated the presence of TSC2 loss of heterozygosity (LOH) in patients with LAM and PLCH. The results showed that TSC2 LOH is not specific to LAM and can also be found in PLCH patients. This suggests that chromosomal abnormalities affecting the TSC2 gene are present in other diseases associated with cancer-like cells.
Article
Medicine, General & Internal
Linli Liu, Chunshui Yu, Gaowu Yan
Summary: This article reports a novel pathological variant in the TSC2 gene that leads to aberrant splicing, confirmed through a minigene assay.
Article
Genetics & Heredity
Lisha Shen, Whenshuai Xu, Jinsong Gao, Jun Wang, Jiannan Huang, Yani Wang, Yudi He, Yanli Yang, Xinlun Tian, Kai-Feng Xu
Summary: Complications such as worsened dyspnea, pneumothorax, and renal angiomyolipoma bleeding were common in LAM patients during pregnancy, especially in those who had been treated with Sirolimus before. Patients with a history of Sirolimus treatment had a higher risk of spontaneous abortion. However, discontinuing Sirolimus before or during pregnancy did not lead to adverse neonatal outcomes for patients without spontaneous abortion.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Multidisciplinary Sciences
Min Qiu, Yan Tang, Jinjin Chen, Rachel Muriph, Zhongfeng Ye, Changfeng Huang, Jason Evans, Elizabeth P. Henske, Qiaobing Xu
Summary: The challenge of delivering mRNA to specific organs and cells in vivo is being addressed, with research showing that N-series LNPs can selectively deliver mRNA to the lungs while O-series LNPs tend to deliver mRNA to the liver. By analyzing the protein corona on targeted LNPs, unique plasma proteins were identified that contribute to their targetability. This research demonstrates the potential of LNPs as a promising therapeutic intervention for lung diseases like lymphangioleiomyomatosis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Anita Maasz, Timea Bodo, Agnes Till, Gabor Molnar, Gyoergy Masszi, Gusztav Labossa, Zsuzsanna Herbert, Judit Bene, Kinga Hadzsiev
Summary: "Impact of Early Genetic Testing and Antiepileptic Drug Therapy on Brain Development." This study presents a three-year follow-up of a patient with tuberous sclerosis complex (TSC) and a utero-detected rhabdomyoma. Genetic testing revealed a de novo variant in the TSC2 gene, and the pregnant mother was treated with everolimus to regress the fetal tumor. Early genetic testing, in utero treatment, and early medication intervention had a significant impact on the developmental delay of the patient.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Critical Care Medicine
Nishant Gupta, Bin Zhang, Yuan Zhou, Francis X. McCormack, Rebecca Ingledue, Nathan Robbins, Elizabeth J. Kopras, Susan McMahan, Abhishek Singla, Jeffrey Swigris, Adam G. Cole, Marina K. Holz
Summary: Is the addition of resveratrol safe and more efficacious than sirolimus alone in patients with lymphangioleiomyomatosis? The addition of resveratrol was found to be safe and well tolerated in patients with lymphangioleiomyomatosis taking sirolimus and was associated with modest improvement in health-related quality of life.
Review
Biochemistry & Molecular Biology
Ekaterina Bychkova, Marina Dorofeeva, Aleksandr Levov, Alexey Kislyakov, Kristina Karandasheva, Vladimir Strelnikov, Kirill Anoshkin
Summary: Patients with tuberous sclerosis complex display cognitive, behavioral, and psychiatric impairments linked to cortical tubers. These tubers are caused by mutations in TSC1 or TSC2 genes, resulting in overactivation of the mTOR pathway. However, the formation of cortical tubers may involve more complex molecular mechanisms that require further investigation.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Eva Revilla-Lopez, Cristina Berastegui, Alejandra Mendez, Berta Saez-Gimenez, Victoria Ruiz de Miguel, Manuel Lopez-Meseguer, Victor Monforte, Carlos Bravo, Miguel Angel Pujana, Maria Antonia Ramon, Susana Gomez-Olles, Antonio Roman
Summary: This study found that sirolimus treatment had a positive long-term effect on most LAM patients, with 59% showing a positive response, 30% showing a partial response, and 11% showing a negative response after 5 years of treatment.
SCIENTIFIC REPORTS
(2021)
Article
Genetics & Heredity
Cong Luo, Ye Zhang, Yu-shi Zhang, Ming-Xin Zhang, Jun Ning, Min-Feng Chen, Yuan Li, Lin Qi, Xiong-Bing Zu, Yang-Le Li, Yi Cai
Summary: This study examines the relationship between genotype and renal phenotype in a Chinese cohort with Tuberous Sclerosis Complex (TSC) and provides guidance for clinical decision-making. The results showed that patients with TSC2 variants are more likely to develop severe renal angiomyolipomas (AML) and require nephrectomy/partial nephrectomy or mTOR medication.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Medicine, General & Internal
Ergin Erginoz, Halit Eren Taskin, Gokce Hande Cavus, Abdullah Kagan Zengin
Summary: Tuberous sclerosis complex is a genetic disorder with manifestations in various organs due to mutations in tumor suppressor genes. Perivascular epithelioid cell tumors, including lymphangioleiomyomatosis, have been linked to these gene mutations. The study presented a case of a 28-year-old woman with multiple manifestations of tuberous sclerosis complex, who underwent surgical procedures for colonic tumor and subsequently developed SARS-CoV-2 infection.
Article
Genetics & Heredity
Hirofumi Kashii, Shinya Kasai, Atsushi Sato, Yoko Hagino, Yasumasa Nishito, Toshiyuki Kobayashi, Okio Hino, Masashi Mizuguchi, Kazutaka Ikeda
Summary: The study found that double mutations in the TSC1 and TSC2 genes lead to the occurrence of autism spectrum disorder, similar to TSC2 mutations. The double mutations cause significant changes in gene expression and contribute to the genotype-phenotype correlations in TSC.
Article
Medicine, General & Internal
Jeong Suk Koh, Sina Oh, Chaeuk Chung
Summary: This article reports a rare case of a patient with systemic lupus erythematosus (SLE) coexisting with pulmonary lymphangioleiomyomatosis (LAM) and renal angiomyolipoma (AML). The patient underwent selective transcatheter embolization for AML and successfully recovered after treatment.
Article
Clinical Neurology
Mario Suzuki, Akihide Kondo, Ikuko Ogino, Osamu Akiyama, Naohide Fujita, Yuzaburo Shimizu, Hajime Arai
Summary: This case report describes a 3-year-old girl with a solitary subependymal giant cell astrocytoma (SEGA) exhibiting histological anaplastic features. Genetic analysis revealed loss of heterozygosity (LOH) in TSC2 in the tumor tissue despite the absence of other clinical manifestations of tuberous sclerosis complex (TSC) in the patient. The high mitotic activity and necrosis observed in the histopathological examination of the tumor make this possibly the first genetically proven case of a solitary SEGA with anaplastic features.
CHILDS NERVOUS SYSTEM
(2021)
Article
Cell Biology
Muireann Ni Bhaoighill, Juan M. Falcon-Perez, Felix Royo, Andrew R. Tee, Jason P. Webber, Elaine A. Dunlop
Summary: This study investigates the role of extracellular vesicles (EVs) in modulating the tumor microenvironment and their impact on the development of TSC tumors. It shows that EVs secreted from TSC2-deficient cells contain a specific protein cargo that promotes cell viability, proliferation, and growth factor secretion in the tumor microenvironment. The study also demonstrates that rapamycin can alter the cargo of EVs and reduce their ability to promote cell proliferation.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Article
Respiratory System
Jesse D. Kirkpatrick, Ava P. Soleimany, Jaideep S. Dudani, Heng-Jia Liu, Hilaire C. Lam, Carmen Priolo, Elizabeth P. Henske, Sangeeta N. Bhatia
Summary: Activity-based nanosensors enable noninvasive, real-time monitoring of disease progression and treatment response in a preclinical model of LAM.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Genetics & Heredity
Victoria E. R. Parker, Kim M. Keppler-Noreuil, Laurence Faivre, Maxime Luu, Neal L. Oden, Leena De Silva, Julie C. Sapp, Katrina Andrews, Marc Bardou, Kong Y. Chen, Thomas N. Darling, Elodie Gautier, Barry R. Goldspiel, Smail Hadj-Rabia, Julie Harris, Georgios Kounidas, Parag Kumar, Marjorie J. Lindhurst, Romaric Loffroy, Ludovic Martin, Alice Phan, Kristina I. Rother, Brigitte C. Widemann, Pamela L. Wolters, Christine Coubes, Lucile Pinson, Marjolaine Willems, Catherine Vincent-Delorme, Pierre Vabres, Robert K. Semple, Leslie G. Biesecker
GENETICS IN MEDICINE
(2019)
Article
Critical Care Medicine
Gustavo Pacheco-Rodriguez, Wendy K. Steagall, Leigh Samsel, Pradeep K. Dagur, J. Philip McCoy, Ilker Tunc, Mehdi Pirooznia, Ji-An Wang, Thomas N. Darling, Joel Moss
Letter
Dermatology
A. M. Treichel, D. J. Kwiatkowski, J. Moss, T. N. Darling
BRITISH JOURNAL OF DERMATOLOGY
(2020)
Editorial Material
Dermatology
T. N. Darling
BRITISH JOURNAL OF DERMATOLOGY
(2020)
Article
Dermatology
Leonard C. Sperling, Benjamin Lockshin, Thomas Darling
JOURNAL OF CUTANEOUS PATHOLOGY
(2020)
Article
Dermatology
Deeti J. Pithadia, John W. Roman, Julie C. Sapp, Leslie G. Biesecker, Thomas N. Darling
Summary: In individuals with Proteus syndrome, asymmetric hypertrichosis on the body and diffuse, scattered, or patchy changes in scalp hair density or color were commonly observed. These findings provide novel insights into the role of PI3K-AKT signaling in skin appendage development.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2021)
Letter
Dermatology
D. J. Pithadia, A. M. Treichel, A. M. Jones, P. Julien-Williams, T. Machado, J. Moss, T. N. Darling
BRITISH JOURNAL OF DERMATOLOGY
(2020)
Letter
Dermatology
Alexander M. Cartron, Alison M. Treichel, Deeti J. Pithadia, Joel Moss, Thomas N. Darling
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2021)
Article
Dermatology
A. M. Cartron, D. Buccine, A. M. Treichel, C. R. Lee, J. Moss, T. N. Darling
Summary: MiF are common skin lesions in TSC patients, mainly located on the back as skin-colored papules. Histological features include dermal expansion and hamartomatous abnormalities. MiF differ from other TSC skin lesions, and recognizing MiF helps define the spectrum of TSC disease.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2021)
Article
Cell Biology
Alison M. Treichel, Deeti J. Pithadia, Chyi-Chia R. Lee, Oyetewa Oyerinde, Joel Moss, Thomas N. Darling
Summary: This study aimed to determine the histopathological features of fibrous cephalic plaques (FCPs) in individuals with tuberous sclerosis complex (TSC), and found thickened collagen bundles and hamartomatous changes involving hair follicles.
Article
Dermatology
Xiong Cai, Qingyuan Fan, Gi Soo Kang, Kelsey Grolig, Xiaoyan Shen, Eric M. Billings, Gustavo Pacheco-Rodriguez, Thomas N. Darling, Joel Moss
Summary: The study suggests that rapamycin may reduce the size of TSC tumors by decreasing TSC2(-/-) cell volume, altering the cell cycle, and reprogramming TSC2-null cells.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Dermatology
Deeti J. Pithadia, Alexander M. Cartron, Leslie G. Biesecker, Thomas N. Darling
Summary: A retrospective review of individuals with genetically confirmed Proteus syndrome revealed a wide spectrum of dermatologic features beyond the previously considered range, which may aid in early diagnosis and management of the condition.
PEDIATRIC DERMATOLOGY
(2021)
Article
Clinical Neurology
Hope Northrup, Mary E. Aronow, E. Martina Bebin, John Bissler, Thomas N. Darling, Petrus J. de Vries, Michael D. Frost, Zoe Fuchs, Elizabeth S. Gosnell, Nishant Gupta, Anna C. Jansen, Sergiusz Jozwiak, J. Chris Kingswood, Timothy K. Knilans, Francis X. McCormack, Ashley Pounders, Steven L. Roberds, David F. Rodriguez-Buritica, Jonathan Roth, Julian R. Sampson, Steven Sparagana, Elizabeth Anne Thiele, Howard L. Weiner, James W. Wheless, Alexander J. Towbin, Darcy A. Krueger
Summary: The diagnostic criteria and management recommendations for tuberous sclerosis complex (TSC) were revised in 2018 based on advancements in knowledge and new therapies since 2013. Changes were made mainly to clinical and genetic diagnostic criteria, as well as surveillance and management standards. These updates aim to provide an improved care framework for individuals with TSC and their families.
PEDIATRIC NEUROLOGY
(2021)
Article
Medicine, Research & Experimental
Katarzyna Klonowska, Joannes M. Grevelink, Krinio Giannikou, Barbara A. Ogorek, Zachary T. Herbert, Aaron R. Thorner, Thomas N. Darling, Joel Moss, David J. Kwiatkowski
Summary: A study found that UV-induced mutations are common in the facial skin of patients with tuberous sclerosis complex (TSC), with an average of 4.8 mutations per 2-mm biopsy. Some of these mutations develop into facial angiofibroma (FAF). The analysis method also identified a new UV-related mutation signature and recurrent complex mutation pattern.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Medicine, Research & Experimental
Kim M. Keppler-Noreuil, Jasmine Burton-Akright, Marjorie J. Lindhurst, Jasmine Shwetar, Julie C. Sapp, Thomas Darling, Leslie G. Biesecker
COLD SPRING HARBOR MOLECULAR CASE STUDIES
(2019)