Article
Cell Biology
Joshua Linnert, Barbara Knapp, Baran E. Gueler, Karsten Boldt, Marius Ueffing, Uwe Wolfrum
Summary: The human Usher syndrome is characterized by progressive vision and hearing loss. Mutations in ADGRV1 and CIB2 genes are associated with two sub-types of Usher syndrome. The proteins encoded by these two genes belong to distinct protein families. The cellular functions of ADGRV1 and CIB2 are still unclear, but they are found to interact with each other and play a role in primary cilia function.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Genetics & Heredity
Talah T. Wafa, Rabia Faridi, Kelly A. King, Christopher Zalewski, Rizwan Yousaf, Julie M. Schultz, Robert J. Morell, Julie Muskett, Amy Turriff, Ekaterini Tsilou, Andrew J. Griffith, Thomas B. Friedman, Wadih M. Zein, Carmen C. Brewer
Summary: Usher syndrome has been traditionally categorized into three classical types based on patient phenotype, but the relationship between vestibular phenotype and Usher gene mutations is not definitive. Research shows that patients with different Usher syndrome types may exhibit varying vestibular dysfunctions, contrary to classical assumptions. Therefore, vestibular phenotyping data may not reliably differentiate between Usher syndrome types.
Article
Physics, Applied
Hideyuki Sugioka, Wataru Tomita, Mitsuhiro Tanaka
Summary: The study demonstrates that a thermally actuated double pendulum can exhibit a metachronal motion using a self-propulsion mechanism caused by spontaneous asymmetrical heat transfer. By using a multiple pendulum structure with beams of different lengths, phase differences can be produced among the beams. This device has potential applications in biomedical microfluidic systems or microrobots in water.
JOURNAL OF APPLIED PHYSICS
(2021)
Article
Ophthalmology
Leonardo Colombo, Paolo E. Maltese, Marco Castori, Said El Shamieh, Christina Zeitz, Isabelle Audo, Alessandra Zulian, Carla Marinelli, Sabrina Benedetti, Alisia Costantini, Simone Bressan, Marcella Percio, Paolo Ferri, Andi Abeshi, Matteo Bertelli, Luca Rossetti
Summary: The study aimed to describe the molecular epidemiology of nonsyndromic retinitis pigmentosa and Usher syndrome in Italian patients. Through genetic analysis, potentially pathogenic variants were identified which have significant implications for disease diagnosis and inheritance mechanisms.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Ophthalmology
Vasily M. Smirnov, Marco Nassisi, Saddek Mohand-Said, Crystel Bonnet, Anne Aubois, Celine Devisme, Thilissa Dib, Christina Zeitz, Natalie Loundon, Sandrine Marlin, Christine Petit, Bahram Bodaghi, Jose-Alain Sahel, Isabelle Audo
Summary: This study provides a detailed phenotypic description of rod-cone dystrophy associated with CLRN1 variants. The retinal phenotype includes visual acuity loss, visual field constriction, and retinal degeneration. Four pathogenic variants were identified in the study.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Lauren Major, Michelle E. McClements, Robert E. MacLaren
Summary: Inherited retinal degenerations are a leading cause of blindness in the UK. Significant advances have been made in tackling this issue, but there are still challenges in delivering gene sequences exceeding the packaging limit and treating toxic gain of function mutations. This article reviews the potential of CRISPR technology in overcoming these challenges.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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)
Review
Medicine, General & Internal
Camron Davies, Jenna Bergman, Carly Misztal, Renuka Ramchandran, Jeenu Mittal, Erdogan Bulut, Viraj Shah, Rahul Mittal, Adrien A. Eshraghi
Summary: Most USH patients benefit from CI, with younger patients generally achieving better outcomes in hearing, speech, and cognition. Prolonged auditory deprivation may lead to poorer performance outcomes post-CI. Further research is needed to understand gene mutations underlying USH pathophysiology for optimal timing of CI.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Ophthalmology
Khine Zaw, Livia S. Carvalho, May T. Aung-Htut, Sue Fletcher, Steve D. Wilton, Fred K. Chen, Samuel McLenachan
Summary: Usher syndrome is the most common form of deaf-blindness, with USH2A being the most prevalent subtype. Patients typically present with hearing loss from birth and develop retinitis pigmentosa in their second decade of life, with no current treatments available to restore vision.
ASIA-PACIFIC JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Cell Biology
Jessica Schaefer, Nicole Wenck, Katharina Janik, Joshua Linnert, Katarina Stingl, Susanne Kohl, Kerstin Nagel-Wolfrum, Uwe Wolfrum
Summary: Human Usher syndrome (USH) is a complex genetic disorder that causes combined deafness and blindness. The underlying mechanisms of the disease, particularly in the eye and retina, are not well understood. This study identifies a role for the scaffold protein harmonin, encoded by the USH1C gene, in regulating the canonical Wnt/beta-catenin signaling pathway. The findings suggest that USH1C/harmonin acts as a suppressor of the pathway, and dysregulation of this pathway may contribute to the development of USH.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Neurosciences
Yi-Chun Hsiao, Jesus Munoz-Estrada, Karina Tuz, Russell J. Ferland
Summary: The Ahi1 gene mutation in mice leads to impaired distribution of MchR1 in cilia, affecting downstream MchR1 signaling pathways, underscoring the importance of cilia as critical signaling centers in neurons.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Endocrinology & Metabolism
Shanat Baig, Subadra Wanninayake, Lukas Foggensteiner, Yasir S. Elhassan, Konstantinos Manolopoulos, Sadaf Ali, Pierre Bel Lassen, Karine Clement, Richard P. Steeds, Jeremy W. Tomlinson, Tarekegn Geberhiwot
Summary: In this study, adipose tissue structure and function were investigated in patients with Bardet-Biedl syndrome (BBS) and obese controls. The results showed that insulin sensitivity and adipose tissue function in BBS patients were similar to those in polygenic obesity, suggesting that the quality and quantity of obesity rather than the duration play a more important role in driving the metabolic phenotype.
INTERNATIONAL JOURNAL OF OBESITY
(2023)
Review
Audiology & Speech-Language Pathology
Eric Nisenbaum, Torin P. Thielhelm, Aida Nourbakhsh, Denise Yan, Susan H. Blanton, Yilai Shu, Karl R. Koehler, Aziz El-Amraoui, Zhengyi Chen, Byron L. Lam, Xuezhong Liu
Summary: Usher syndrome is a group of disorders characterized by hearing loss, vestibular dysfunction, and vision loss. It is divided into three clinical subtypes and is associated with numerous genes. The relationship between genotype and phenotype may vary depending on the mutation location and type. Understanding these relationships is crucial for the development of gene-based therapies.
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.
Article
Geriatrics & Gerontology
Marta Del Pozo-Valero, Marta Corton, Rosario Lopez-Rodriguez, Ignacio Mahillo-Fernandez, Javier Ruiz-Hornillos, Pablo Minguez, Cristina Villaverde, Maria Elena Perez-Tomas, Maria Barreda-Sanchez, Esther Mancebo, Estela Paz-Artal, Encarna Guillen-Navarro, Berta Almoguera, Carmen Ayuso
Summary: This study reveals the association between clonal hematopoiesis and mortality in COVID-19 patients, particularly showing a significant correlation between pathogenic/likely pathogenic clonal hematopoiesis and mortality in the 75-84 age group.
Article
Genetics & Heredity
Francisco Martinez-Granero, Elena Martinez-Cayuelas, Cristina Rodilla, Gonzalo Nunez-Moreno, Marta Rodriguez de Alba, Fiona Blanco-Kelly, Raquel Romero, Pablo Minguez, Carmen Ayuso, Isabel Lorda-Sanchez, Marta Corton, Berta Almoguera
Summary: Joubert syndrome (JS) is a clinically and genetically heterogeneous genetic disorder. We identified a novel biallelic intragenic duplication of exons 20-46 of CPLANE1 in a case of JS, which is the first report of such duplication as a potential molecular mechanism of JS. The diagnosis was confirmed by brain MRI showing the molar tooth sign, consistent with JS.
Article
Ophthalmology
Natalia Lorenzana-Blanco, Belen Jimenez-Rolando, Blanca Garcia-Sandoval, Fiona Blanco-Kelly, Almudena Avila-Fernandez, Inmaculada Martin-Merida, Milagros Garcia-Ferreira, Silvia Campos-Seco, Carmen Ayuso, Ester Carreno
Summary: Multicolour reflectance images (MCI) play an important role in the phenotypic diagnosis of inherited retinal disorders (IRDs), helping to highlight clinical features and guide genetic diagnosis.
EUROPEAN JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alejandra Tamayo, Gonzalo Nunez-Moreno, Carolina Ruiz, Julie Plaisancie, Alejandra Damian, Jennifer Moya, Nicolas Chassaing, Patrick Calvas, Carmen Ayuso, Pablo Minguez, Marta Corton
Summary: PAX6 haploinsufficiency causes aniridia, a congenital eye disorder that involves the iris, and foveal hypoplasia. Comprehensive screening of the PAX6 locus revealed four deep-intronic variants with potential effects on pre-RNA splicing. Functional analysis using in vitro minigene splicing assays and nanopore-based long-read sequencing confirmed the impact of two variants on aberrant splicing, while the other two variants were found to have no effect on splicing. This study emphasizes the importance of integrating functional studies into diagnostic algorithms to achieve conclusive genetic diagnoses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lorena de la Fuente, Marta Del Pozo-Valero, Irene Perea-Romero, Fiona Blanco-Kelly, Lidia Fernandez-Caballero, Marta Corton, Carmen Ayuso, Pablo Minguez
Summary: Screening for pathogenic variants in rare genetic diseases has become more comprehensive with the use of whole exome and genome sequencing. However, the gene-disease associations are still not fully known. In this study, the researchers compiled functional networks and observed their varying ability to recover genes associated with different genetic diseases. They developed a network-based algorithm, GLOWgenes, which showed promising results in identifying new gene-disease associations, especially for less obvious ones.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Elena Martinez-Cayuelas, Fiona Blanco-Kelly, Fermina Lopez-Grondona, Saoud Tahsin Swafiri, Rosario Lopez-Rodriguez, Rebeca Losada-Del Pozo, Ignacio Mahillo-Fernandez, Beatriz Moreno, Maria Rodrigo-Moreno, Didac Casas-Alba, Aitor Lopez-Gonzalez, Sixto Garcia-Minaur, Maria Angeles Mori, Marta Pacio-Minguez, Emi Rikeros-Orozco, Fernando Santos-Simarro, Jaime Cruz-Rojo, Juan Francisco Quesada-Espinosa, Maria Teresa Sanchez-Calvin, Jaime Sanchez-Del Pozo, Raquel Bernado Fonz, Maria Isidoro-Garcia, Irene Ruiz-Ayucar, Maria Isabel Alvarez-Mora, Raquel Blanco-Lago, Begona De Azua, Jesus Eiris, Juan Jose Garcia-Penas, Belen Gil-Fournier, Carmen Gomez-Lado, Nadia Irazabal, Vanessa Lopez-Gonzalez, Irene Madrigal, Ignacio Malaga, Beatriz Martinez-Menendez, Soraya Ramiro-Leon, Maria Garcia-Hoyos, Pablo Prieto-Matos, Javier Lopez-Pison, Sergio Aguilera-Albesa, Sara Alvarez, Alberto Fernandez-Jaen, Isabel Llano-Rivas, Blanca Gener-Querol, Carmen Ayuso, Ana Arteche-Lopez, Maria Palomares-Bralo, Anna Cueto-Gonzalez, Irene Valenzuela, Antonio Martinez-Monseny, Isabel Lorda-Sanchez, Berta Almoguera
Summary: This study investigated 67 patients with KBG syndrome and proposed new clinical diagnostic criteria based on the findings.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Genetics & Heredity
Richard Holt, David Goudie, Alejandra Damian Verde, Alice Gardham, Francis Ramond, Audrey Putoux, Ajoy Sarkar, Virginia Clowes, Jill Clayton-Smith, Siddharth Banka, Laura Cortazar Galarza, Gilles Thuret, Marta Ubeda Erviti, Ane Zurutuza Ibarguren, Raquel Saez Villaverde, Alejandra Tamayo Duran, Carmen Ayuso, Dorine A. Bax, Julie Plaisancie, Marta Corton, Nicolas Chassaing, Patrick Calvas, Nicola K. Ragge
Summary: In this study, variants in the FZD5 gene were found to be associated with ocular coloboma and rare cases of microphthalmia. The presence of additional syndromic features and variable penetrance suggests that extraocular phenotypes may be explained by alterations in other genes.
OPHTHALMIC GENETICS
(2022)
Article
Multidisciplinary Sciences
A. Arteche-Lopez, A. Avila-Fernandez, R. Riveiro Alvarez, B. Almoguera, A. Bustamante Aragones, I Martin-Merida, M. A. Lopez Martinez, A. Gimenez Pardo, C. Velez-Monsalve, J. Gallego Merlo, I Garcia Vara, F. Blanco-Kelly, S. Tahsin Swafiri, I Lorda Sanchez, M. J. Trujillo Tiebas, C. Ayuso
Summary: Exome sequencing is an effective tool for genetic diagnosis, but it only provides a molecular diagnosis in a limited number of cases. In this study, we evaluated the diagnostic rate of clinical exomes and found that it varied depending on the type of disease. We also identified common mutated genes and discussed further investigations needed.
SCIENTIFIC REPORTS
(2022)
Article
Andrology
Rosario Lopez-Rodriguez, Javier Ruiz-Hornillos, Marta Corton, Berta Almoguera, Pablo Minguez, Maria Elena Perez-Tomas, Maria Barreda-Sanchez, Esther Mancebo, Lorena Ondo, Andrea Martinez-Ramas, Lidia Fernandez-Caballero, Juan Carlos Taracido-Fernandez, Antonio Herrero-Gonzalez, Ignacio Mahillo, Estela Paz-Artal, Encarna Guillen-Navarro, Carmen Ayuso
Summary: There is no association between the androgen receptor polyQ polymorphism and the severity of COVID-19 in male patients.
Correction
Biochemistry & Molecular Biology
Yesim Kesim, Fabiola Ceroni, Alejandra Damian, Fiona Blanco-Kelly, Carmen Ayuso, Kathy Williamson, Veronique Paquis-Flucklinger, Dorine A. Bax, Julie Plaisancie, Claudine Rieubland, Mostafa Chamlal, Marta Corton, Nicolas Chassaing, Patrick Calvas, Nicola K. Ragge
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Yesim Kesim, Fabiola Ceroni, Alejandra Damian, Fiona Blanco-Kelly, Carmen Ayuso, Kathy Williamson, Veronique Paquis-Flucklinger, Dorine A. Bax, Julie Plaisancie, Claudine Rieubland, Mostafa Chamlal, Marta Corton, Nicolas Chassaing, Patrick Calvas, Nicola K. Ragge
Summary: Biallelic pathogenic variants in ALDH1A3 account for 11% of recessively inherited severe developmental eye anomalies. The relationship between ALDH1A3 variants and variable neurodevelopmental features remains unclear. This study describes seven unrelated families with biallelic pathogenic ALDH1A3 variants, confirming the consistent manifestation of bilateral anophthalmia/microphthalmia (A/M) with additional neurodevelopmental features and significant variability. Additionally, the study highlights the importance of screening ALDH1A3 variants in nonconsanguineous families with A/M and reports the first case with cataract.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Tamar Hayman, Talya Millo, Karen Hendler, Itay Chowers, Menachem Gross, Eyal Banin, Dror Sharon
Summary: This study conducted whole exome sequencing (WES) on 491 unsolved cases of Inherited Retinal Diseases (IRDs) in Israeli and Palestinian families, identifying the genetic cause of the disease in 51% of cases, with 11% attributed to CNVs. The analysis also identified potential new genes, ESRRB and DNM1.
JOURNAL OF MEDICAL GENETICS
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Marta del Pozo-Valero, Rosa Riveiro-Alvarez, Inmaculada Martin-Merida, Fiona Blanco-Kelly, Saoud Swafiri, Isabel Lorda-Sanchez, M. Jose Trujillo-Tiebas, Ester Carreno, Belen Jimenez-Rolando, Blanca Garcia-Sandoval, Marta Corton, Almudena Avila-Fernandez, Carmen Ayuso
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Richard J. Holt, David Goudie, Ajoy Sarkar, Alejandra Damian, Alejandra Tamayo, Carmen Ayuso, Marta Corton, Alice Gardham, Virginia Clowes, Julie Plaisancie, Nicolas Chassaing, Patrick Calvas, Nicola K. Ragge
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Samer Khateb, Aya Shemesh, Ashly Offenheim, Ruth Sheffer, Tamar Ben-Yosef, Itay Chowers, Rina Leibu, Britta Baumann, Bernd Wissinger, Susanne Kohl, Eyal Banin, Dror Sharon
Summary: This study aimed to investigate the clinical, genetic, and electrophysiological characteristics of a specific form of Blue Cone Monochromacy (BCM) caused by mutations in the OPN1LW/OPN1MW genes. The results showed that patients with these mutations exhibited milder symptoms, improved visual acuity, more severe myopia, and higher 30-Hz cone flicker responses compared to the typical BCM group.