Article
Genetics & Heredity
Urszula Smyczynska, Marcin Stanczak, Miljan Kuljanin, Aneta Wlodarczyk, Ewelina Stoczynska-Fidelus, Joanna Taha, Bartlomiej Pawlik, Maciej Borowiec, Joseph D. D. Mancias, Wojciech Mlynarski, Piotr Rieske, Wojciech Fendler, Agnieszka Zmyslowska
Summary: This study conducted transcriptomic and proteomic analysis on cellular models of Alstrom syndrome and Bardet-Biedl syndrome, identifying common and distinct pathological mechanisms between the two syndromes. Genes related to lipid and glycosaminoglycan metabolism and small molecule transport were downregulated, while those associated with signal transduction, immune system, cell cycle control, and DNA replication and repair were upregulated. Protein pathways involved in autophagy, apoptosis, cilium assembly, and Gli1 protein were also upregulated in both syndromes.
Review
Nutrition & Dietetics
Avital Horwitz, Ruth Birk
Summary: Obesity is a metabolic state characterized by the expansion of adipose tissue, which is regulated by genetics and excess energy intake. While the genetic regulation of adipose tissue expansion is not fully understood, studies on both monogenic and syndromic obesity have identified several genes related to obesity. Syndromic obesity, such as Bardet-Biedl syndrome (BBS), involves additional features and provides insights into peripheral adipocyte regulation in obesity. This review summarizes current knowledge on adipocyte hyperplasia and hypertrophy in common obesity and highlights the importance of studying syndromic obesity models like BBS.
Article
Endocrinology & Metabolism
Samantha E. Day, Yunhua L. Muller, Cigdem Koroglu, Sayuko Kobes, Kim Wiedrich, Darin Mahkee, Hye In Kim, Cris Van Hout, Nehal Gosalia, Bin Ye, Alan R. Shuldiner, William C. Knowler, Robert L. Hanson, Clifton Bogardus, Leslie J. Baier
Summary: This study reports potentially functional variants in BBS genes in American Indians, but the functional evidence supporting a causal role for BBS9 in obesity is inconclusive.
Article
Cell Biology
Xiaohong Meng, Yanling Long, Jiayun Ren, Gang Wang, Xin Yin, Shiying Li
Summary: This study identified five known and twelve novel variants in four BBS genes in 10 Chinese families with BBS, expanding the variation spectrum of the disease. The ocular characteristics of BBS patients were clinically highly heterogeneous, emphasizing the usefulness of a combination of ffERG and FVEP assessments in evaluating visual function in the advanced stage of retinopathy in BBS.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Endocrinology & Metabolism
Agnieszka Zmyslowska, Urszula Smyczynska, Marcin Stanczak, Krzysztof Jeziorny, Agnieszka Szadkowska, Wojciech Fendler, Maciej Borowiec
Summary: This study found that patients with ALMS and BBS syndromes have different circulating miRNA expressions compared to obese individuals and controls. Additionally, eight miRNAs were found to be associated with the course of these diseases.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Genetics & Heredity
Elizabeth Forsythe, Usha G. Mallya, Min Yang, Caroline Huber, Mary Lynn Cala, Alexandra Greatsinger, Ella Hagopian, Jeremy Pomeroy, Andrea M. Haqq
Summary: This study aimed to quantify the caregiver burden associated with Bardet-Biedl syndrome (BBS), a rare obesity syndrome. The results showed that the symptoms of BBS, particularly hyperphagia, had a negative impact on caregiver mood, sleep, and relationships. Caregivers also experienced personal strain, family impact, and financial burden.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Review
Pediatrics
Tommaso La Macchia, Alessio Mancuso, Maria Domenica Ceravolo, Caterina Cuppari, Roberto Chimenz, Giovanni Farello, Eloisa Gitto, Giulia Iapadre, Ida Ceravolo
Summary: Alstrom syndrome is a rare multisystem disorder characterized by vision loss, hearing deficiency, obesity, type 2 diabetes mellitus, and insulin resistance. It can also lead to cardiac, pulmonary, renal, hepatic, and endocrinological dysfunctions. Early identification of the disease can help slow down its progression and improve the patient's quality of life.
JOURNAL OF PEDIATRIC NEUROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Xiumin Yan, Yidong Shen
Summary: Primary cilia are important sensory organelles in cells, with intraflagellar transport essential for their assembly, maintenance, and function. Recent studies have highlighted the critical regulatory roles of three ciliary Rab-like small GTPases in ciliary BBSome transport.
Article
Genetics & Heredity
Brais Bea-Mascato, Carlos Solarat, Irene Perea-Romero, Teresa Jaijo, Fiona Blanco-Kelly, Jose M. Millan, Carmen Ayuso, Diana Valverde
Summary: Alstrom syndrome is an ultra-rare disease caused by mutations in the ALMS1 gene, leading to a range of symptoms. Two novel pathogenic mutations were discovered in homozygosis, along with a probable founder effect in three unrelated families.
Article
Pediatrics
Ana Simicic Majce, Darija Tudor, Marko Simunovic, Marko Todorovic, Mladenka Parlov, Bernarda Lozic, Mirna Saraga-Babic, Marijan Saraga, Adela Arapovic
Summary: Bardet-Biedl syndrome (BBS) is a rare genetic syndrome caused by mutations in genes responsible for primary cilia. This case report highlights the diversity in clinical expression and renal impairment in a family with BBS caused by a rare mutation. The study emphasizes the importance of genetic analysis in timely diagnosis and prevention of long-term complications in patients with BBS.
FRONTIERS IN PEDIATRICS
(2023)
Article
Ophthalmology
Wan-Yu Cheng, Mei-Jiao Ma, Shi-Qin Yuan, Xiao-Long Qi, Wei-Ning Rong, Xun-Lun Sheng
Summary: In this study, two novel compound heterozygous pathogenic variants of the ALMS1 gene were identified in three patients with Alstrom Syndrome from two Chinese families, expanding the genotypic and phenotypic spectrums of ALMS1-AS. The study highlights the significance of genetic testing in aiding the clinical diagnosis of cases with phenotypic diversities, enabling early diagnosis and treatment to prevent future systemic damage in AS patients.
Article
Medicine, General & Internal
Chunmei Wang, Xiaona Luo, Yilin Wang, Zhao Liu, Shengnan Wu, Simei Wang, Xiaoping Lan, Quanmei Xu, Wuhen Xu, Fang Yuan, Anqi Wang, Fanyi Zeng, Jia Jia, Yucai Chen
Summary: Alstrom syndrome is a genetic disease caused by a mutation in the ALMS1 gene, characterized by multisystem involvement. Whole-exome sequencing plays an important role in diagnosing this disease. This study discovered two novel variants of the ALMS1 gene, expanding the understanding of Alstrom syndrome.
Article
Multidisciplinary Sciences
Rui-Kai Zhang, Wei-Yue Sun, Yan-Xia Liu, Emma Y. Zhang, Zhen-Chuan Fan
Summary: This study reveals the mechanism of signal protein export from cilia via the RABL2-ARL3 cascade-mediated outward BBSome transition zone diffusion pathway.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Yan-Xia Liu, Wen -Juan Li, Rui-Kai Zhang, Sheng-Nan Sun, Zhen-Chuan Fan
Summary: Certain ciliary signaling proteins are transported from the tip to the base of cilia via retrograde intraflagellar transport (IFT), facilitated by the BBSome and ARL13. The interaction between ARL13GTP and BBS3GTP at the ciliary tip plays a crucial role in properly coupling the BBSome with signaling cargo. This understanding provides mechanistic insights into the defects seen in hedgehog signaling in humans with ARL13b and BBS3 mutations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Ophthalmology
Tianchang Tao, Jia Liu, Bin Wang, Jijing Pang, Xiaoxin Li, Lvzhen Huang
Summary: This study detected and analyzed pathogenic variants in four Chinese families with BBS. Four novel gene mutations were identified, expanding the genotypic spectrum of BBS.
EUROPEAN JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Loretta De Chiara, Virginia Leiro-Fernandez, Mar Rodriguez-Girondo, Diana Valverde, Maria Isabel Botana-Rial, Alberto Fernandez-Villar
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Multidisciplinary Sciences
Irene Perea-Romero, Gema Gordo, Ionut F. Iancu, Marta Del Pozo-Valero, Berta Almoguera, Fiona Blanco-Kelly, Ester Carreno, Belen Jimenez-Rolando, Rosario Lopez-Rodriguez, Isabel Lorda-Sanchez, Inmaculada Martin-Merida, Lucia Perez de Ayala, Rosa Riveiro-Alvarez, Elvira Rodriguez-Pinilla, Saoud Tahsin-Swafiri, Maria J. Trujillo-Tiebas, Blanca Garcia-Sandoval, Pablo Minguez, Almudena Avila-Fernandez, Marta Corton, Carmen Ayuso
Summary: This study investigated the genetic landscape of inherited retinal diseases (IRDs) in Spain, involving 6089 patients from 4403 unrelated families. The most common phenotype identified was retinitis pigmentosa (RP), with several genes such as PRPH2, ABCA4, and RS1 being recurrently mutated across different types of IRD.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Maria Alvarez-Satta, Mauro Lago-Docampo, Brais Bea-Mascato, Carlos Solarat, Sheila Castro-Sanchez, Soren T. Christensen, Diana Valverde
Summary: This study reveals that ALMS1 depletion affects ciliary morphology and TGF-beta/BMP signaling, shedding light on its role in primary cilia function and cellular signaling, potentially linking it to the pathology of Alstrom syndrome.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Medicine, General & Internal
Marta Nunez-Fernandez, Cristina Ramos-Hernandez, Francisco Garcia-Rio, Maria Torres-Duran, Andres Nodar-Germinas, Amara Tilve-Gomez, Paula Rodriguez-Fernandez, Diana Valverde-Perez, Alberto Ruano-Ravina, Alberto Fernandez-Villar
Summary: A study found that the most frequent alteration in respiratory function tests three to four months after hospitalization for COVID-19 pneumonia was decreased DLCO. Factors associated with changes in DLCO-DLNO combination included age, gender, dyspnoea severity, perception of health, and physical capacity.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Cell Biology
Ignacio Hernandez-Gonzalez, Jair Tenorio-Castano, Nuria Ochoa-Parra, Natalia Gallego, Carmen Perez-Olivares, Mauro Lago-Docampo, Julian Palomino Doza, Diana Valverde, Pablo Lapunzina, Pilar Escribano-Subias
Summary: This study identified genetic defects in patients with CTD-PAH, with disease-associated variants observed in 9 patients, including pathogenic variants in genes such as TBX4, ABCC8, KCNA5, and GDF2/BMP9. These findings suggest that genetic factors may play a role in Pulmonary Vascular Disease (PVD) in CTD patients.
Article
Genetics & Heredity
Mariana G. Lopez, Alvaro Chiner-Oms, Dario Garcia de Viedma, Paula Ruiz-Rodriguez, Maria Alma Bracho, Irving Cancino-Munoz, Giuseppe D'Auria, Griselda de Marco, Neris Garcia-Gonzalez, Galo Adrian Goig, Inmaculada Gomez-Navarro, Santiago Jimenez-Serrano, Llucia Martinez-Priego, Paula Ruiz-Hueso, Lidia Ruiz-Roldan, Manuela Torres-Puente, Juan Alberola, Eliseo Albert, Maitane Aranzamendi Zaldumbide, Maria Pilar Bea-Escudero, Jose Antonio Boga, Antoni E. Bordoy, Andres Canut-Blasco, Ana Carvajal, Gustavo Cilla Eguiluz, Maria Luz Cordon Rodriguez, Jose J. Costa-Alcalde, Maria de Toro, Inmaculada de Toro Peinado, Jose Luis del Pozo, Sebastian Duchene, Jovita Fernandez-Pinero, Begona Fuster Escriva, Concepcion Gimeno Cardona, Veronica Gonzalez Galan, Nieves Gonzalo Jimenez, Silvia Hernaez Crespo, Marta Herranz, Jose Antonio Lepe, Carla Lopez-Causape, Jose Luis Lopez-Hontangas, Vicente Martin, Elisa Martro, Ana Milagro Beamonte, Milagrosa Montes Ros, Rosario Moreno-Munoz, David Navarro, Jose Maria Navarro-Mari, Anna Not, Antonio Oliver, Begona Palop-Borras, Monica Parra Grande, Irene Pedrosa-Corral, Maria Carmen Perez Gonzalez, Laura Perez-Lago, Mercedes Perez-Ruiz, Luis Pineiro Vazquez, Nuria Rabella, Antonio Rezusta, Lorena Robles Fonseca, Sara Sanbonmatsu-Gamez, Jon Sicilia, Alex Soriano, Maria Dolores Tirado Balaguer, Ignacio Torres, Alexander Tristancho, Jose Maria Marimon, Mireia Coscolla, Fernando Gonzalez-Candelas, Inaki Comas
Summary: This study sequenced 2,170 samples from the first wave of the COVID-19 epidemic in Spain, identifying at least 500 introductions of SARS-CoV-2 variants from multiple international sources and documenting the early rise of two dominant Spanish epidemic clades. The research shows that public health interventions effectively reduced the reproductive number of these clades, leading to the replacement of the dominant variants by a new variant over the summer of 2020.
Article
Virology
Pilar Gallego-Garcia, Nair Varela, Nuria Estevez-Gomez, Loretta De Chiara, Iria Fernandez-Silva, Diana Valverde, Nicolae Sapoval, Todd J. Treangen, Benito Regueiro, Jorge Julio Cabrera-Alvargonzalez, Victor del Campo, Sonia Perez, David Posada
Summary: Understanding the transmission of SARS-CoV-2 is crucial for effective prevention measures. This study investigated the effectiveness of genomic sequencing in inferring transmission events. The research found that intrahost genomic variation in SARS-CoV-2 is limited, making it difficult to identify direct transmission events. The slow mutation rate, convergent events, and technical artifacts hinder the reliable reconstruction of transmission based solely on genomic data. Detailed contact tracing is essential for studying SARS-CoV-2 transmission at a high resolution.
Article
Cardiac & Cardiovascular Systems
Mauro Lago-Docampo, Carlos Solarat, Luis Mendez-Martinez, Adolfo Baloira, Diana Valverde
Summary: Pulmonary Arterial Hypertension (PAH) is a rare disease caused by the obliteration of the pulmonary arterioles, leading to right heart failure. Endothelin-1 (EDN1) is a peptide that constricts blood vessels and its levels are associated with disease progression in PAH. In this study, we sequenced the untranslated regions of EDN1 in PAH patients and identified two single nucleotide polymorphisms (SNPs) that can affect gene expression. We found that the transcription factors PPAR gamma, KLF4, and VDR can bind to these SNPs and regulate EDN1 production in different cell types.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Critical Care Medicine
Matina Prapa, Mauro Lago-Docampo, Emilia M. Swietlik, David Montani, Melanie Eyries, Marc Humbert, Carrie L. Welch, Wendy K. Chung, Rolf M. F. Berger, Harm Jan Bogaard, Olivier Danhaive, Pilar Escribano-Subias, Henning Gall, Barbara Girerd, Ignacio Hernandez-Gonzalez, Simon Holden, David Hunt, Samara M. A. Jansen, Wilhelmina Kerstjens-Frederikse, David G. Kiely, Pablo Lapunzina, John McDermott, Shahin Moledina, Joanna Pepke-Zaba, Gary J. Polwarth, Gwen Schotte, Jair Tenorio-Castano, A. A. Roger Thompson, John Wharton, Stephen J. Wort, Karyn Megy, Rutendo Mapeta, Carmen M. Treacy, Jennifer M. Martin, Wei Li, Andrew J. Swift, Paul D. Upton, Nicholas W. Morrell, Stefan Graf, Diana Valverde
Summary: This study analyzed TBX4-associated pulmonary arterial hypertension and found that TBX4 variants can cause both loss-of-function and gain-of-function effects. The differential impact of pathogenic mutations located in critical protein domains may explain the pleiotropic effects of TBX4 in lung disease.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Genetics & Heredity
Irene Perea-Romero, Carlos Solarat, Fiona Blanco-Kelly, Iker Sanchez-Navarro, Brais Bea-Mascato, Eduardo Martin-Salazar, Isabel Lorda-Sanchez, Saoud Tahsin Swafiri, Almudena Avila-Fernandez, Inmaculada Martin-Merida, Maria Jose Trujillo-Tiebas, Ester Carreno, Belen Jimenez-Rolando, Blanca Garcia-Sandoval, Pablo Minguez, Marta Corton, Diana Valverde, Carmen Ayuso
Summary: This study aimed to investigate the role of mutational load in the clinical variability of Bardet-Biedl syndrome (BBS). Through clinical annotation and mutational load analysis, it was found that mutations in multiple BBS-associated genes may be associated with a more severe phenotype and specific clinical features. The study also revealed the potential role of oligogenic inheritance in BBS.
NPJ GENOMIC MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Jesus Eduardo Martin-Salazar, Diana Valverde
Summary: Primary cilia, non-motile organelles associated with the cell cycle, are formed through various mechanisms and are linked to gene complexes. Genetic defects can lead to faulty cilium formation and the occurrence of ciliopathies.
Article
Multidisciplinary Sciences
Isaura Fernandez Perez, Diana Valverde, Concepcion Fiano Valverde, Jenifer Brea Iglesias, Maria Jose Villanueva Silva, Martin Lazaro Quintela, Barbara Melendez
Summary: In the treatment decision-making for low-grade gliomas (LGG), clinical criteria like EORTC and RTOG are still being used despite the introduction of molecular features. However, the consistency between EORTC and RTOG criteria is low, indicating the need to integrate clinical-molecular scores for improved treatment decisions.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Brais Bea-Mascato, Elena Neira-Goyanes, Antia Iglesias-Rodriguez, Diana Valverde
Summary: The research demonstrates that the ALMS1 gene plays a role in controlling the cell cycle and apoptosis processes. Depletion of ALMS1 affects the signal transduction through the TGF-beta pathway and other processes like cell migration and adhesion capacity.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Alejandro Cruz-Utrilla, Natalia Gallego-Zazo, Carmen Perez-Olivares, Ignacio Hernandez-Gonzalez, Pedro Bedate, Amaya Martinez Menaca, Manuel Lopez Meseguer, Pablo Lapunzina, Marta Perez Nunez, Nuria Ochoa Parra, Diana Valverde, Jair Antonio Tenorio-Castano, Pilar Escribano-Subias
Summary: This study analyzed the genetic testing results of 298 patients with pulmonary arterial hypertension and incorporated genetic information into the current risk assessment model. The study found that although genetic information did not significantly improve the overall prognostic evaluation, it could better identify patients at intermediate-low and intermediate-high risk. This is of great significance for optimizing treatment strategies and improving patient prognosis.
REVISTA ESPANOLA DE CARDIOLOGIA
(2023)
Article
Biochemistry & Molecular Biology
Alba Vera-Zambrano, Mauro Lago-Docampo, Natalia Gallego, Juan Felipe Franco-Gonzalez, Daniel Morales-Cano, Alejandro Cruz-Utrilla, Marta Villegas-Esguevillas, Edgar Fernandez-Malave, Pilar Escribano-Subias, Jair Antonio Tenorio-Castano, Francisco Perez-Vizcaino, Diana Valverde, Teresa Gonzalez, Angel Cogolludo
Summary: Reduced expression and/or activity of Kv1.5 channels is a common feature in PAH. This study characterized seven KCNA5 variants found in PAH patients and found that two of them resulted in loss of channel function and reduced expression, affecting cell apoptosis. These findings suggest that KCNA5 variants may be causative or contributing factors for PAH.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)