Article
Medicine, General & Internal
Andres Moreno-De-Luca, Francisca Millan, Denis R. Pesacreta, Houda Z. Elloumi, Matthew T. Oetjens, Claire Teigen, Karen E. Wain, Julie Scuffins, Scott M. Myers, Rebecca I. Torene, Vladimir G. Gainullin, Kevin Arvai, H. Lester Kirchner, David H. Ledbetter, Kyle Retterer, Christa L. Martin
Summary: The molecular diagnostic yield of exome sequencing among patients with cerebral palsy was found to be 32.7% in a cohort of pediatric patients and 10.5% in a cohort of adult patients. Further research is needed to understand the clinical implications of these findings. This study provides insights into the prevalence of pathogenic and likely pathogenic variants detected in children and adults with cerebral palsy undergoing genetic testing through exome sequencing.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2021)
Review
Acoustics
M. Pauta, R. J. Martinez-Portilla, A. Borrell
Summary: This study compares the diagnostic yield of exome or genome sequencing (ES/GS) with chromosomal microarray analysis (CMA) in fetuses with increased nuchal translucency (NT). The results show a 4% incremental diagnostic yield of ES/GS over CMA in fetuses with increased NT and no concomitant anomalies. Additionally, some fetuses may have genetic disorders such as Noonan syndrome.
ULTRASOUND IN OBSTETRICS & GYNECOLOGY
(2022)
Article
Clinical Neurology
Amjad Khan, Anne Molitor, Sylvain Mayeur, Gaoqun Zhang, Bruno Rinaldi, Beatrice Lannes, Benoit Lhermitte, Muhammad Umair, Stefan T. Arold, Sylvie Friant, Sepand Rastegar, Mathieu Anheim, Seiamak Bahram, Raphael Carapito
Summary: A novel missense variant in the PPP1R1B gene was identified in a consanguineous family with generalized dystonia. The expression of PPP1R1B protein in movement control regions suggests its involvement in abnormal movements, making it a potential gene to be sequenced in patients with unexplained movement disorders.
MOVEMENT DISORDERS
(2022)
Article
Clinical Neurology
Michael Zech, Robert Jech, Sylvia Boesch, Matej Skorvanek, Jan Necpal, Jana Svantnerova, Matias Wagner, Ariane Sadr-Nabavi, Felix Distelmaier, Martin Krenn, Tereza Serranova, Irena Rektorova, Petra Havrankova, Alexandra Mosejova, Iva Prihodova, Jana Sarlakova, Kristina Kulcsarova, Olga Ulmanova, Karel Bechyne, Miriam Ostrozovicova, Vladimir Han, Joaquim Ribeiro Ventosa, Theresa Brunet, Riccardo Berutti, Mohammad Shariati, Ali Shoeibi, Susanne A. Schneider, Alice Kuster, Matthias Baumann, David Weise, Friederike Wilbert, Wibke G. Janzarik, Matthias Eckenweiler, Volker Mall, Bernhard Haslinger, Steffen Berweck, Juliane Winkelmann, Konrad Oexle
Summary: The algorithm for dystonia diagnosis based on individual phenotypic aspects showed the highest diagnostic yield when the total score was 5. The sensitivity and specificity for implementing WES at the threshold of 3 points were 96% and 52% respectively.
MOVEMENT DISORDERS
(2021)
Article
Genetics & Heredity
Frederic Tran Mau-Them, Julian Delanne, Anne-Sophie Denomme-Pichon, Hana Safraou, Ange-Line Bruel, Antonio Vitobello, Aurore Garde, Sophie Nambot, Nicolas Bourgon, Caroline Racine, Arthur Sorlin, Sebastien Moutton, Nathalie Marle, Thierry Rousseau, Paul Sagot, Emmanuel Simon, Catherine Vincent-Delorme, Odile Boute, Cindy Colson, Florence Petit, Marine Legendre, Sophie Naudion, Caroline Rooryck, Clement Prouteau, Estelle Colin, Agnes Guichet, Alban Ziegler, Dominique Bonneau, Godelieve Morel, Melanie Fradin, Alinoe Lavillaureix, Chloe Quelin, Laurent Pasquier, Sylvie Odent, Gabriella Vera, Alice Goldenberg, Anne-Marie Guerrot, Anne-Claire Brehin, Audrey Putoux, Jocelyne Attia, Carine Abel, Patricia Blanchet, Constance F. Wells, Caroline Deiller, Mathilde Nizon, Sandra Mercier, Marie Vincent, Bertrand Isidor, Jeanne Amiel, Rodolphe Dard, Manon Godin, Nicolas Gruchy, Mederic Jeanne, Elise Schaeffer, Pierre-Yves Maillard, Frederique Payet, Marie-Line Jacquemont, Christine Francannet, Sabine Sigaudy, Marine Bergot, Emilie Tisserant, Marie-Laure Ascencio, Christine Binquet, Yannis Duffourd, Christophe Philippe, Laurence Faivre, Christel Thauvin-Robinet
Summary: This study describes the implementation of exome sequencing in prenatal diagnosis in France after the detection of anomalies on prenatal ultrasound. The study found that trio-exome sequencing provided a high diagnostic yield with a median turnaround time of 28 days. Trio-exome sequencing and chromosomal microarray analysis were concordant for identifying pathogenic CNVs.
FRONTIERS IN GENETICS
(2023)
Review
Genetics & Heredity
Maria Juliana Ballesta-Martinez, Virginia Perez-Fernandez, Vanesa Lopez-Gonzalez, Maria Jose Sanchez-Soler, Ana Teresa Serrano-Anton, Lidia Isolina Rodriguez-Pena, Maria Barreda-Sanchez, Lluis Armengol-Dulcet, Encarna Guillen-Navarro
Summary: Intellectual disability (ID) affects 1-3% of the population, with approximately 30-50% of cases having a genetic cause. Next-generation sequencing has provided high diagnostic potential for ID patients. This study evaluated the diagnostic yield and economic impact of clinical exome sequencing in 188 ID patients, highlighting a significant diagnostic yield (34%) and reduced costs and time to diagnosis. The findings support the early implementation of clinical exome sequencing in the diagnostic workup of ID patients in clinical practice.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Article
Obstetrics & Gynecology
Karin E. M. Diderich, Kathleen Romijn, Marieke Joosten, Lutgarde C. P. Govaerts, Marike Polak, Hennie T. Bruggenwirth, Martina Wilke, Marjon A. van Slegtenhorst, Yolande van Bever, Alice S. Brooks, Grazia M. S. Mancini, Ingrid M. B. H. van de Laar, Joan N. R. Kromosoeto, Maarten F. C. M. Knapen, Attie T. J. Go, Diane Van Opstal, Lies H. Hoefsloot, Robert-Jan H. Galjaard, Malgorzata Srebniak
Summary: This retrospective cohort study demonstrated that prenatal whole exome sequencing, when offered by a clinical geneticist in addition to chromosomal microarray testing, significantly increased the diagnostic yield in fetuses with ultrasound anomalies, allowing for early detection of genetic disorders.
ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA
(2021)
Review
Genetics & Heredity
Montse Pauta, Raigam J. Martinez-Portilla, Eva Meler, Juan Otano, Antoni Borrell
Summary: The aim of this study was to assess the diagnostic yield of exome sequencing (ES) in fetuses with isolated fetal growth restriction (FGR), compared to chromosomal microarray analysis (CMA) or karyotyping. The study included selected research that focused on FGR without fetal structural anomalies and had negative CMA or karyotype results. The results showed that ES had an incremental diagnostic performance of 12% in identifying pathogenic variants associated with isolated FGR.
PRENATAL DIAGNOSIS
(2023)
Article
Genetics & Heredity
Ataf H. Sabir, Elizabeth Morley, Jameela Sheikh, Alistair D. Calder, Ana Beleza-Meireles, Moira S. Cheung, Alessandra Cocca, Mattias Jansson, Suzanne Lillis, Yogen Patel, Shu Yau, Christine M. Hall, Amaka C. Offiah, Melita Irving
Summary: This study utilized whole-exome sequencing (WES) for molecular diagnosis in skeletal dysplasia (SD) cases, finding a certain proportion of patients with definite or likely molecular diagnoses. In fact, the greatest diagnostic return occurred in cases where the diagnosis was known pre-test.
BMC MEDICAL GENOMICS
(2021)
Article
Biochemistry & Molecular Biology
Lucas Andre Cavalcanti Brandao, Ronald Rodrigues de Moura, Angelo Valerio Marzano, Chiara Moltrasio, Paola Maura Tricarico, Sergio Crovella
Summary: Unravelling the molecular basis of multifactorial disorders requires new genomic analysis tools that focus on disrupted pathways rather than associated gene variants, as association studies have limitations in understanding the interactions between disease-causing variants. In this study, Variant Enrichment Analysis (VEA) was developed and applied to identify novel pathways altered in patients with complex autoinflammatory skin disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Maria Isabel Alvarez-Mora, Aurora Sanchez, Laia Rodriguez-Revenga, Jordi Corominas, Raquel Rabionet, Susana Puig, Irene Madrigal
Summary: This study aims to discuss the impact and advantages of implementing NGS in the diagnosis of NDDs. The results show that NGS technology can better identify pathogenic gene mutations and suggest that NGS should be used as the first-choice diagnostic method for NDDs.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Review
Acoustics
M. Pauta, R. J. Martinez-Portilla, A. Borrell
Summary: This study aimed to determine the diagnostic yield of exome sequencing in fetuses with multisystem structural anomalies. The results showed that exome sequencing was able to identify potentially causative genes in up to one-third of cases where chromosomal microarray analysis or karyotyping had failed to do so.
ULTRASOUND IN OBSTETRICS & GYNECOLOGY
(2022)
Article
Clinical Neurology
Barbara Garavaglia, Sadeq Vallian, Luigi M. Romito, Giulia Straccia, Marianna Capecci, Federica Invernizzi, Elisa Andrenelli, Arezu Kazemi, Sylvia Boesch, Robert Kopajtich, Nahid Olfati, Mohammad Shariati, Ali Shoeibi, Ariane Sadr-Nabavi, Holger Prokisch, Juliane Winkelmann, Michael Zech
Summary: This study reports the role of AOPEP gene in recessive forms of generalized dystonia and dystonia-parkinsonism, suggesting that AOPEP variants are a major cause of dystonic movement-disorder phenotypes worldwide.
PARKINSONISM & RELATED DISORDERS
(2022)
Article
Genetics & Heredity
Meihua Tan, Xinrui Wang, Hongjie Liu, Xiaoyan Peng, You Yang, Haifei Yu, Liangpu Xu, Jia Li, Hua Cao
Summary: Congenital heart disease (CHD) is a common malformation in fetuses and neonates, and a leading cause of mortality. Genetic mechanisms behind CHD remain poorly understood and many patients lack a genetic diagnosis. In this study, a strategy combining low-coverage whole-genome sequencing and whole-exome sequencing was used to identify genetic causes of CHD. By analyzing a patient-only cohort, 34.71% of CHD patients were diagnosed with genetic causes, with chromosomal abnormalities and damaging variants of CHD-related genes being common findings. Eight candidate CHD-causing genes were identified, along with 86 potential CHD-related genes. Our study provides new insights into the research strategies and underlying mechanisms of CHD.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Go Hun Seo, Hane Lee, Jungsul Lee, Heonjong Han, You Kyung Cho, Minji Kim, Yunha Choi, Jeongmin Choi, In Hee Choi, Seonkyeong Rhie, Kyu Young Chae, Yoo-Mi Kim, Chong Kun Cheon, Su Jin Kim, Jieun Lee, Eungu Kang, Jung Hye Byeon, Hee Joon Yu, Young-Lim Shin, Arum Oh, Woo Jin Kim, Mi-Sun Yum, Beom Hee Lee, Baik-Lin Eun
Summary: Daily updated databases and reanalysis systems enhance the diagnostic performance in patients with NDD/ID, contributing to the rapid diagnosis of undiagnosed patients by applying the latest molecular genetic information.
MOLECULAR MEDICINE
(2022)
Article
Clinical Neurology
Jun-Pyo Hong, Hanim Kwon, Euyhyun Park, Sun-Uk Lee, Chan-Nyoung Lee, Byung-Jo Kim, Ji-Soo Kim, Kun-Woo Park
Summary: In patients with mild-to-moderate PD, vestibular function assessed by video head-impulse tests appears relatively preserved and has minimal impact on the risk of falls. Risk of postural instability is associated with the severity of clinical symptoms in PD.
PARKINSONISM & RELATED DISORDERS
(2024)
Article
Clinical Neurology
Yaqin Xiang, XiuRong Huang, Qian Xu, Zhenhua Liu, Yase Chen, Qiying Sun, Junling Wang, Hong Jiang, Lu Shen, Xinxiang Yan, Beisha Tang, Jifeng Guo
Summary: Using the novel data-driven method DEBM, this study determined the sequence of several common biomarker changes in Parkinson's disease (PD). The left putamen was found to be the earliest biomarker to become abnormal, followed by the right putamen, CSF alpha-synuclein, right caudate, left caudate, and serum NfL. The estimated disease stages showed significant differences between PD and healthy controls, and achieved a high accuracy for distinguishing PD from HC.
PARKINSONISM & RELATED DISORDERS
(2024)
Article
Clinical Neurology
Yan Li, David J. McLernon, Carl E. Counsell, Angus D. Macleod
Summary: This study aimed to investigate the incidence and risk factors for institutionalisation in Parkinson's disease (PD) and atypical parkinsonism (AP). The study found that institutionalisation was more frequent in AP compared to PD and controls. Age, poorer cognition, and more-severe parkinsonian impairment were independent predictors of institutionalisation.
PARKINSONISM & RELATED DISORDERS
(2024)
