Article
Genetics & Heredity
Kui Hu, Yun Wan, Fu-Tsuen Lee, Jinmiao Chen, Hao Wang, Haonan Qu, Tao Chen, Wang Lu, Zhenwei Jiang, Lufang Gao, Xiaojuan Ji, Liqun Sun, Daokang Xiang
Summary: This study reports an intronic variant in the fibrillin 1 (FBN1) gene that affects RNA splicing in a patient with Marfan syndrome. The findings highlight the importance of considering exon/intron boundaries and conducting functional analysis in the assessment of whole-exome sequencing (WES) results.
FRONTIERS IN GENETICS
(2022)
Article
Medicine, General & Internal
Su Hyun Yoon, Younghwa Kong
Summary: Neonatal Marfan syndrome is rare and severe, presenting with a range of clinical features affecting multiple systems. Despite medical management, the progression of cardiac issues in neonatal MFS can be severe and may lead to early death.
Review
Genetics & Heredity
James Jiqi Wang, Bo Yu, Yang Sun, Xiuli Song, Dao Wen Wang, Zongzhe Li
Summary: We reported a novel splice-altering mutation in the FBN1 gene that leads to two abnormal transcripts simultaneously. By systematically summarizing previous transcriptional studies of splice-altering mutations, we gained further insights into the clinical and transcriptional consequences of these mutations.
Article
Genetics & Heredity
Xin Liu, Kaiqing Liu, Danyao Nie, Jing Zhang, Liyun Zhang, Xinhua Liu, Jiantao Wang
Summary: In this study, we investigated the effects of cysteine mutations in different domains of fibrillin-1 on protein stability and found that mutations in the EGF domain have a greater impact on proteolytic sensitivity and thermostability compared to mutations in the cbEGF domain. Furthermore, cysteine mutations can result in the exposure or alteration of enzymatic sites. These results suggest that cysteine mutations in fibrillin-1 may play a significant role in the pathogenesis of diseases such as Marfan syndrome.
FRONTIERS IN GENETICS
(2022)
Article
Medicine, General & Internal
Dandan Li, Jun Qiao, Dandan Huang, Ruru Guo, Jian Ji, Wei Liu
Summary: In this study, whole exome sequencing and Sanger sequencing were used to identify a novel and a recurrent missense mutation in FBN1 in two Chinese families with Marfan syndrome (MFS). Bioinformatics analysis confirmed the pathogenicity of these mutations. The findings expand the mutation spectrum of FBN1 and contribute to a better understanding of the genetic defects in MFS patients.
FRONTIERS IN MEDICINE
(2022)
Article
Oncology
Yanyu Duan, Haiying Chang, Jiayuan Ling, Shaoqiang Liu, Yiming Zhong
Summary: This study aims to further understand Marfan syndrome by analyzing the clinical manifestation of a novel FBN1 variant. The FBN1 variant c.5081_5082insT (p.Leu1694fs*9) was found to be a pathogenic mutation associated with early-onset familial thoracic aortic aneurysms in MFS patients.
ANNALS OF TRANSLATIONAL MEDICINE
(2021)
Article
Genetics & Heredity
Yuri A. Zarate, Shaine A. Morris, Anna Blackshare, Claudia A. Algaze, Brynn S. Connor, Andrew J. Kim, Katherine E. Yutzey, Erin M. Miller, Kathryn Nicole Weaver, Ronnie Thomas Collins
Summary: This study aimed to develop objective diagnostic criteria for early onset Marfan syndrome (eoMFS) to facilitate early diagnosis and timely interventions. The researchers developed an age-based, diagnostic scoring system based on extensive literature review and expert survey responses. The study found that individuals with eoMFS had significantly higher cardiac, systemic, and FBN1 scores compared to those without eoMFS, and a proposed clinical score cutoff showed excellent sensitivity, specificity, and reliability.
GENETICS IN MEDICINE
(2022)
Review
Genetics & Heredity
Anthony Piscopo, Taylor Warner, Jaime Nagy, Vidya Nagrale, Aaron Stence, Natalya Guseva, John A. Bernat, Amy Calhoun
Summary: This is a case report of a 16-month-old female with early-onset Marfan syndrome caused by an 11.2 kb de novo duplication in the FBN1 gene. The duplication was confirmed to be in tandem through optical genome mapping, genetic sequencing, and chromosomal microarray. This is the third reported case of a large multi-exon duplication in FBN1, and the only one confirmed to be in tandem. This finding expands the landscape of known FBN1 pathogenic variants and supports the use of genetic testing strategies that can detect large, indel-type variants.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Biochemistry & Molecular Biology
Cristina M. M. Sulea, Zsolt Martonfalvi, Csilla Csanyi, Dora Haluszka, Miklos Polos, Bence Agg, Roland Stengl, Kalman Benke, Zoltan Szabolcs, Miklos S. Z. Kellermayer
Summary: Fibrillin-1 microfibrils are crucial for the extracellular matrix, providing support for elastin deposition and giving connective tissues strength and elasticity. Mutations in the FBN1 gene are associated with Marfan syndrome, a connective tissue disorder characterized by aortic complications. In this study, microfibrils from aortic samples with FBN1 mutations and non-MFS aortic samples were compared using atomic force microscopy. The MFS microfibrils showed a thinner and potentially more fragile structure, which may contribute to MFS-related aortic symptoms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Laure Delhon, Zakaria Mougin, Jeremie Jonquet, Angelique Bibimbou, Johanne Dubail, Cynthia Bou-Chaaya, Nicolas Goudin, Wilfried Le Goff, Catherine Boileau, Valerie Cormier-Daire, Carine Le Goff
Summary: Mutations in the FBN1 gene can cause short stature and other symptoms similar to GD. This study used a knock-in mouse model to investigate the role of the TB5 domain in bone development and found that FBN1 mutations affect chondrocyte differentiation and growth plate formation, leading to GD.
HUMAN MOLECULAR GENETICS
(2022)
Review
Endocrinology & Metabolism
Kim M. Summers, Stephen J. Bush, Margaret R. Davis, David A. Hume, Sahar Keshvari, Jennifer A. West
Summary: Fibrillin-1 serves as a component of extracellular microfibrils and plays a role in connective tissues' elasticity. It has been found that a peptide derived from fibrillin-1, called asprosin, functions as a glucogenic hormone during fasting and stimulates appetite in the hypothalamus. Asprosin levels are associated with metabolic syndrome-related pathologies. The relationship between the generation of asprosin and the expression of fibrillin-1 protein needs further exploration.
MOLECULAR GENETICS AND METABOLISM
(2023)
Review
Genetics & Heredity
Pauline Arnaud, Zakaria Mougin, Catherine Boileau, Carine Le Goff
Summary: Fibrillinopathies encompass a group of diseases with mutations in fibrillin genes. Marfan syndrome is the most well-known condition, with other disorders such as geleophysic/acromicric dysplasias exhibiting different features. ADAMTSL proteins play a significant role in the pathogenic mechanisms of these disorders.
FRONTIERS IN GENETICS
(2021)
Review
Genetics & Heredity
Mehmet Akif Ovali, Ibrahim Bozgeyik
Summary: Asprosin is a novel protein hormone that promotes hepatic glucose release and appetite stimulation, and is encoded by the penultimate 2 exons of the FBN1 gene. It interacts with its G protein-coupled receptor, OR4M1, to regulate various physiological processes, and is implicated in the development of conditions such as diabetes, obesity, cardiomyopathy, cancer, and polycystic ovarian syndrome. Asprosin plays a key role in maintaining energy metabolism homeostasis.
MOLECULAR SYNDROMOLOGY
(2022)
Article
Ophthalmology
Dongwei Guo, Liyan Liu, Kit Yee Ng, Qianzhong Cao, Danying Zheng, Xinyu Zhang, Guangming Jin
Summary: This study explores the ocular and cardiovascular characteristics of children with Marfan syndrome and related fibrillinopathies, as well as their association with genotype. The results show that children with FBN1 mutations involving cysteine substitution or mutations in exons 22-42, as well as those with long axial length, have higher risks of severe cardiovascular complications. Nearly half of the children with congenital ectopia lentis were diagnosed with cardiovascular disease for the first time.
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2023)
Article
Multidisciplinary Sciences
Sacha A. Jensen, Ondine Atwa, Penny A. Handford
Summary: The human FBN1 gene encodes fibrillin-1, the main component of extracellular matrix microfibrils, with mutations in FBN1 causing Marfan syndrome. Variants associated with neonatal MFS showed reduced microfibril incorporation compared to classic MFS variants, indicating disruption in microfibril assembly. This study identified new requirements for microfibril biogenesis and distinct molecular mechanisms linked to disease substitutions in the TB3-cbEGF18 region, shedding light on the pathogenesis of Marfan syndrome.
Article
Obstetrics & Gynecology
Antonin Sipek, Vladimir Gregor, Antonin Sipek, Jan Klaschka, Marek Maly, Pavel Calda
Summary: This study analyzed the screening results of a population with a high rate of first-trimester screening and a low rate of cell-free DNA testing for chromosomal aberrations. The study found an increase in major autosomal trisomies and a decrease in other chromosomal aberrations, as well as a reduction in the use of invasive diagnostic procedures.
JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
(2022)
Article
Immunology
Juraj Bosak, Matej Lexa, Kristyna Fiedorova, Darshak C. Gadara, Lenka Micenkova, Zdenek Spacil, Jiri Litzman, Tomas Freiberger, David Smajs
Summary: CVID patients exhibit an expanded bacterial diversity and dysregulation in metabolic pathways in the gut microbiome, indicating potential diagnostic and prognostic markers for CVID in the future.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Microbiology
Iva Kotaskova, Vit Syrovatka, Hana Obrucova, Petra Videnska, Barbora Zwinsova, Veronika Hola, Eva Blastikova, Filip Ruzicka, Tomas Freiberger
Summary: The study analyzed the prevalence of A. schaalii in urine samples, finding that A. schaalii-positive samples were more diverse and related to other bacteria. A. schaalii may be associated with certain bacterial species, while being mutually exclusive with others.
Article
Genetics & Heredity
Joana R. Chora, Michael A. Iacocca, Lukas Tichy, Hannah Wand, C. Lisa Kurtz, Heather Zimmermann, Annette Leon, Maggie Williams, Steve E. Humphries, Amanda J. Hooper, Mark Trinder, Liam R. Brunham, Alexandre Costa Pereira, Cinthia E. Jannes, Margaret Chen, Jessica Chonis, Jian Wang, Serra Kim, Tami Johnston, Premysl Soucek, Michal Kramarek, Sarah E. Leigh, Alain Carrie, Eric J. Sijbrands, Robert A. Hegele, Tomas Freiberger, Joshua W. Knowles, Mafalda Bourbon
Summary: This study provides consensus recommendations for the classification of LDLR variants in Familial Hypercholesterolemia (FH) based on modified guidelines. The establishment of these guidelines as the new standard can improve the accuracy and consistency of LDLR variant classification, thereby enhancing the care of patients with FH.
GENETICS IN MEDICINE
(2022)
Article
Medicine, General & Internal
Tycho R. Tromp, Merel L. Hartgers, G. Kees Hovingh, Antonio J. Vallejo-Vaz, Kausik K. Ray, Handrean Soran, Tomas Freiberger, Stefano Bertolini, Mariko Harada-Shiba, Dirk J. Blom, Frederick J. Raal, Marina Cuchel
Summary: Patients with homozygous familial hypercholesterolaemia (HoFH) globally face issues of late diagnosis, under-treatment, and high risk of premature ASCVD. The use of multiple lipid-lowering therapy regimens is associated with lower LDL cholesterol levels and better outcomes. Significant global disparities exist in treatment regimens, control of LDL cholesterol levels, and cardiovascular event-free survival.
Article
Clinical Neurology
Jitka Majovska, Anita Hennig, Igor Nestrasil, Susanne A. Schneider, Helena Jahnova, Manuela Vaneckova, Martin Magner, Petr Dusek
Summary: Late-onset Tay-Sachs disease is a rare autosomal recessive neurodegenerative disorder characterized by slowly progressive cerebellar ataxia, lower motor neuron disease, and psychiatric impairment. On brain MRI, pontocerebellar atrophy is a constant finding in LOTS patients. These characteristic clinical and MRI findings can help in the differential diagnosis of adult-onset cerebellar ataxias.
NEUROLOGICAL SCIENCES
(2022)
Article
Genetics & Heredity
Martin Reboun, Jakub Sikora, Martin Magner, Helena Wiederlechnerova, Alena Cerna, Helena Poupetova, Gabriela Storkanova, Dita Musalkova, Gabriela Dostalova, Lubor Golan, Ales Linhart, Lenka Dvorakova
Summary: This study aimed to evaluate X-chromosome inactivation (XCI) testing in female Fabry disease (FD) patients. The results showed that combining multiple testing methods generates more reliable results, correlating XCI with gene expression and enzyme activity helps identify crossover events, and age and tissue-specific patterns should be considered.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Genetics & Heredity
Anna Tylki-Szymanska, Zsuzsanna Almassy, Violetta Christophidou-Anastasiadou, Daniela Avdjieva-Tzavella, Ingeborg Barisic, Rimante Cerkauskiene, Goran Cuturilo, Maja Djiordjevic, Zoran Gucev, Anna Hlavata, Beata Kiec-Wilk, Martin Magner, Ivan Pecin, Vasilica Plaiasu, Mira Samardzic, Dimitrios Zafeiriou, Ioannis Zaganas, Christina Lampe
Summary: This study analyzed the management and treatment of mucopolysaccharidoses (MPS), a group of lysosomal storage disorders, in Southern and Eastern European countries. The results showed that the region has a high number of MPS patients and a high level of care. However, there are challenges in implementing enzyme replacement therapy (ERT) and conducting certain assessments due to a lack of skilled specialists. The study suggests simplifying the availability and reimbursement of ERT and implementing educational programs for specialists.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Genetics & Heredity
Hana Stufkova, Hana Kolarova, Katerina Lokvencova, Tomas Honzik, Jiri Zeman, Hana Hansikova, Marketa Tesarova
Summary: In this study, a new pathogenic variant in mitochondrial DNA was discovered, associated with symptoms including myoclonus, epilepsy, muscle weakness, and hearing impairment. The variant was found in the MTTK gene with a mutation load ranging from 71% to >96% in tested tissues. The study also revealed decreased respiratory chain complex activities in muscle mitochondria. This finding expands the spectrum of MTTK variants associated with mitochondrial encephalopathies in adults.
Review
Health Care Sciences & Services
Lorena Diaz-Ordonez, Estephania Candelo, Katherine Silva-Cuero, Wilmar Saldarriaga, Lenka Murgasova, Martin Magner, Harry Pachajoa
Summary: This scoping review aims to understand the evidence regarding the pathophysiology, classification, epidemiology, and clinical management of hearing loss in MPS IVA patients, as well as the effect of therapy for hearing loss. The review will gather relevant literature and analyze the data for descriptive reporting.
JMIR RESEARCH PROTOCOLS
(2022)
Article
Genetics & Heredity
Maria Lucia Cediel, Michal Stawarski, Xavier Blanc, Lenka Noskova, Martin Magner, Konrad Platzer, Janina Gburek-Augustat, Dustin Baldridge, John N. Constantino, Emmanuelle Ranza, Bernhard Bettler, Stylianos E. Antonarakis
Summary: GABA(B) receptors are responsible for neuronal inhibition in the central nervous system. Variants in GABBR2 have been associated with certain phenotypes, while no phenotypes have been established for GABBR1 variants. This study identified four GABBR1 variants in individuals with motor and/or language delay, and functional characterization revealed their impact on GABA potency and efficacy, providing insights into disease severity and potential therapeutic strategies.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Endocrinology & Metabolism
John J. Mitchell, Barbara K. Burton, Michael B. Bober, Philippe M. Campeau, Shelda Cohen, Sara Dosenovic, Carolyn Ellaway, Kaustuv Bhattacharya, Nathalie Guffon, David Hinds, Alice Lail, Shuan-Pei Lin, Martin Magner, Julian Raiman, Liat Schwartz-Sagi, Karolina M. Stepien
Summary: The Morquio A Registry Study (MARS) is an ongoing multinational observational study that aims to characterize the disease heterogeneity and natural history of MPS IVA and evaluate the long-term effectiveness and safety of elosulfase alfa enzyme replacement therapy (ERT). The study has enrolled 381 subjects from 17 countries, and the data collected over the first 6 years show that ERT treatment can stabilize endurance and respiratory function without new safety concerns.
MOLECULAR GENETICS AND METABOLISM
(2022)
Review
Cardiac & Cardiovascular Systems
Samuel S. Gidding, Albert Wiegman, Urh Groselj, Tomas Freiberger, Noel Peretti, Kanika Dharmayat, Magdalena Daccord, Nicola Bedlington, Jaka Sikonja, Kausik K. Ray, Raul D. Santos, Martin Halle, Lale Tokgozoglu, Inaki Gutierrez-Ibarluzea, Fausto J. Pinto, Marius Geanta
Summary: Familial hypercholesterolaemia (FH) is often overlooked and undertreated in Europe, resulting in increased risk of premature heart disease. Early treatment is effective in preventing heart disease and cost-effective. The European Commission Public Health Best Practice Portal recognizes FH screening as an effective strategy. Model programs in Europe employ cascade screening, universal screening, opportunistic screening, or a combination of these approaches to identify young individuals with FH. Recommendations to improve FH identification emphasize the need for screening programs in every country, adapted to fit the healthcare system, with financial support from governments and further research for optimization.
EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
(2022)
Article
Genetics & Heredity
Susan M. Hiatt, Slavica Trajkova, Matteo Rossi Sebastiano, E. Christopher Partridge, Fatima E. Abidi, Ashlyn Anderson, Muhammad Ansar, Stylianos E. Antonarakis, Azadeh Azadi, Ruxandra Bachmann-Gagescu, Andrea Bartuli, Caroline Benech, Jennifer L. Berkowitz, Michael J. Betti, Alfredo Brusco, Ashley Cannon, Giulia Caron, Yanmin Chen, Meagan E. Cochran, Tanner F. Coleman, Molly M. Crenshaw, Laurence Cuisset, Cynthia J. Curry, Hossein Darvish, Serwet Demirdas, Maria Descartes, Jessica Douglas, David A. Dyment, Houda Zghal Elloumi, Giuseppe Ermondi, Marie Faoucher, Emily G. Farrow, Stephanie A. Felker, Heather Fisher, Anna C. E. Hurst, Pascal Joset, Melissa A. Kelly, Stanislav Kmoch, Benjamin R. Leadem, Michael J. Lyons, Marina Macchiaiolo, Martin Magner, Giorgia Mandrile, Francesca Mattioli, Megan McEown, Sarah K. Meadows, Livija Medne, Naomi J. L. Meeks, Sarah Montgomery, Melanie P. Napier, Marvin Natowicz, Kimberly M. Newberry, Marcello Niceta, Lenka Noskova, Catherine B. Nowak, Amanda G. Noyes, Matthew Osmond, Eloise J. Prijoles, Jada Pugh, Verdiana Pullano, Chloe Quelin, Simin Rahimi-Aliabadi, Anita Rauch, Sylvia Redon, Alexandre Reymond, Caitlin R. Schwager, Elizabeth A. Sellars, Angela E. Scheuerle, Elena Shukarova-Angelovska, Cara Skraban, Elliot Stolerman, Bonnie R. Sullivan, Marco Tartaglia, Isabelle Thiffault, Kevin Uguen, Luis A. Umana, Yolande van Bever, Saskia N. van der Crabben, Marjon A. van Slegtenhorst, Quinten Waisfisz, Camerun Washington, Lance H. Rodan, Richard M. Myers, Gregory M. Cooper
Summary: Using the MatchMaker Exchange, researchers identified rare protein-altering variations in the ZMYM3 gene in a cohort of 27 individuals with neurodevelopmental disorders (NDDs). These variations affected protein structure and function and were associated with developmental delay, intellectual disability, behavioral abnormalities, and specific facial features. The evidence from evolutionary conservation, protein modeling, and functional experiments strongly supports ZMYM3 as an NDD-associated gene.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Nutrition & Dietetics
Martin Magner, Katerina Thorova, Veronika Zupova, Milan Houska, Ivana Svandova, Pavla Novotna, Jan Triska, Nadezda Vrchotova, Ivo Soural, Ladislav Jilek
Summary: This study examined the effects of sulforaphane on autistic behavior in children aged 3-7 years with autism spectrum disorder. However, the results showed no significant improvement in the behavioral outcome measures after 36 weeks of treatment with sulforaphane.