Article
Biochemistry & Molecular Biology
Lucia Pia Bruno, Gabriella Doddato, Floriana Valentino, Margherita Baldassarri, Rossella Tita, Chiara Fallerini, Mirella Bruttini, Caterina Lo Rizzo, Maria Antonietta Mencarelli, Francesca Mari, Anna Maria Pinto, Francesca Fava, Alessandra Fabbiani, Vittoria Lamacchia, Anna Carrer, Valentina Caputo, Stefania Granata, Elisa Benetti, Kristina Zguro, Simone Furini, Alessandra Renieri, Francesca Ariani
Summary: Intelectual disability (ID) and autism spectrum disorder (ASD) are often associated and characterized by impairments in cognitive processes and daily life tasks. Molecular diagnosis is crucial for improving prognosis and initiating treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Theresa Brunet, Robert Jech, Melanie Brugger, Reka Kovacs, Bader Alhaddad, Gloria Leszinski, Korbinian M. Riedhammer, Dominik S. Westphal, Isabella Mahle, Katharina Mayerhanser, Matej Skorvanek, Sandrina Weber, Elisabeth Graf, Riccardo Berutti, Jan Necpal, Petra Havrankova, Petra Pavelekova, Maja Hempel, Urania Kotzaeridou, Georg F. Hoffmann, Steffen Leiz, Christine Makowski, Timo Roser, Sebastian A. Schroeder, Robert Steinfeld, Gertrud Strobl-Wildemann, Julia Hoefele, Ingo Borggraefe, Felix Distelmaier, Tim M. Strom, Juliane Winkelmann, Thomas Meitinger, Michael Zech, Matias Wagner
Summary: Up to 40% of neurodevelopmental disorders have a documented underlying monogenic defect, primarily due to de novo variants. The study showed an overall diagnostic yield of 49.8%, with de novo variants contributing to more than 80% of all solved cases. Additionally, novel disease genes and potential pathogenic variants were identified in this research.
Article
Neurosciences
Bo Yuan, Mengdi Wang, Xinran Wu, Peipei Cheng, Ran Zhang, Shunying Yu, Jie Zhang, Yasong Du, Xiaoqun Wang, Zilong Qiu
Summary: In this study, whole-exome sequencing was used to examine Chinese individuals with autism spectrum disorder (ASD) and their parents. The researchers identified a large number of de novo mutations and copy number variations related to ASD. They also found that genes with these de novo mutations were specifically expressed in certain regions of the human brain, and that ASD patients had structural and functional abnormalities in these brain regions.
NEUROSCIENCE BULLETIN
(2023)
Article
Pediatrics
Karthika Ajit Valaparambil, Alfiya Fasaludeen, Lakshmi Priya, Ramshekhar N. Menon, Ramesh Menon, Soumya Sundaram
Summary: This study aimed to evaluate the utility of clinical exome sequencing (CES) in children with neurodevelopmental disorders (NDDs) in India. The findings showed that CES could effectively diagnose pathogenic and likely pathogenic variants, with a diagnostic yield of 41%.
INDIAN JOURNAL OF PEDIATRICS
(2023)
Article
Pediatrics
Michelle van Slobbe, Arie van Haeringen, Lisenka E. L. M. Vissers, Emilia K. Bijlsma, Julie W. Rutten, Manon Suerink, Esther A. R. Nibbeling, Claudia A. L. Ruivenkamp, Saskia Koene
Summary: This study evaluated the yield of whole-exome sequencing (WES) reanalysis in standard patient care in the Netherlands and found that it significantly increased the genetic diagnosis rate for patients. Most newly diagnosed patients had clinical consequences, and patients with dysmorphic features had a higher diagnostic yield in WES reanalysis.
EUROPEAN JOURNAL OF PEDIATRICS
(2023)
Article
Clinical Neurology
Leonie von Elsner, Guoliang Chai, Pauline E. Schneeberger, Frederike L. Harms, Christian Casar, Minyue Qi, Malik Alawi, Ghada M. H. Abdel-Salam, Maha S. Zaki, Florian Arndt, Xiaoxu Yang, Valentina Stanley, Maja Hempel, Joseph G. Gleeson, Kerstin Kutsche
Summary: The peripheral protein FRA10AC1 of the spliceosomal C complex plays a crucial role in neurodevelopment, with mutations potentially leading to intellectual disabilities and other symptoms.
Article
Clinical Neurology
Pauline E. Schneeberger, Sheela Nampoothiri, Tess Holling, Dhanya Yesodharan, Malik Alawi, A. S. Knisely, Thomas Mueller, Barbara Plecko, Andreas R. Janecke, Kerstin Kutsche
Summary: GARP and EARP are membrane-tethering heterotetramers located at the trans-Golgi network and recycling endosomes, mediating retrograde transport and endocytic recycling. Patients with VPS50 variants exhibit severe developmental delay, microcephaly, seizures, and liver abnormalities.
Review
Genetics & Heredity
Giuseppe Donato Mangano, Antonina Fontana, Vincenzo Antona, Vincenzo Salpietro, Giuseppa Renata Mangano, Mario Giuffre, Rosaria Nardello
Summary: This study aims to analyze the similarities and differences of voltage-gated sodium channels Nav1.2 and Nav1.6 in neurodevelopmental disorders. An observational study was conducted on two patients with neurodevelopment disorders, analyzing and comparing their demographic, electroclinical, genetic, and neuropsychological characteristics with those reported in the literature. The study suggests that the neurodevelopmental disorders without epilepsy in these patients may be a result of loss of function of Nav1.2/Nav1.6 channels, with different severity depending on the variant involved.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2022)
Review
Pediatrics
Juliann M. Savatt, Scott M. Myers
Summary: The article discusses the importance and efficiency of genetic testing in patients with neurodevelopmental disorders, and suggests that genetic testing should be offered to all patients with specific symptoms. However, data show that only a minority of children with autism spectrum disorder and intellectual disability have undergone genetic testing.
FRONTIERS IN PEDIATRICS
(2021)
Article
Medical Laboratory Technology
Wenqiu Zhang, Li Hu, Xinyi Huang, Dan Xie, Jiangfen Wu, Xiaoling Fu, Daiyi Liang, Shengwen Huang
Summary: This study identified five novel de novo mutations from four known ID-causing genes in four pediatric patients with unexplained intellectual disability (ID). These mutations were predicted to be deleterious and were located at highly conserved domains, potentially affecting the structure and function of these proteins.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2022)
Article
Genetics & Heredity
Hannaleena Kokkonen, Auli Siren, Tuomo Maatta, Magda Kamila Kadlubowska, Anushree Acharya, Liz M. Nouel-Saied, Suzanne M. Leal, Irma Jarvela, Isabelle Schrauwen
Summary: The study identified unique inherited microduplications at Xp21.2 and Xq13.1 in two families with neurodevelopmental disorders. Patients with Xq13.1 duplication exhibited delayed speech development, mild intellectual disability, facial dysmorphism, heart defects, and neuropsychiatric symptoms, while those with Xp21.2 duplication presented delayed speech development, mild to moderate intellectual disability, strabismus, and neurobehavioral symptoms. Comprehensive clinical and genetic examination of X-chromosome microduplications can aid in diagnosis of neurodevelopmental diseases.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Psychology, Developmental
Taeyeop Lee, Hyeji Lee, Soowhee Kim, Kee Jeong Park, Joon-Yong An, Hyo-Won Kim
Summary: This study aimed to investigate the genetic variations that contribute to the early neurodevelopmental outcomes in developmental disabilities (DDs). Through exome sequencing, it was found that the improvement group, compared to the non-improvement group, had a lower number of risk variants in known DD genes and haploinsufficient genes, as well as an overall lower number of putative risk variants. These findings provide a preliminary basis for developing a sequencing analysis model that predicts clinical outcomes.
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
(2022)
Article
Medicine, General & Internal
Yu-Xiong Guo, Hong-Xia Ma, Yu-Xin Zhang, Zhi-Hong Chen, Qiong-Xiang Zhai
Summary: This study recruited 21 IDD patients and found that the majority of them had moderate IDD, with 8 patients having seizures and 4 patients exhibiting characteristics of autism. Eleven different variants were identified, with no significant differences in the functional areas results between the gene-positive and gene-negative groups.
INTERNATIONAL JOURNAL OF GENERAL MEDICINE
(2021)
Review
Medicine, General & Internal
Carla Lintas, Roberto Sacco, Alessia Azzara, Ilaria Cassano, Fiorella Gurrieri
Summary: The advancement of NGS technologies has significantly improved ASD genetic diagnosis, leading to the discovery of many new causative genes. A recent study revealed 30 novel genes, with 6 of them providing important clinical and molecular data that can aid clinical geneticists in prioritizing and interpreting genetic tests. This new information may help in associating genetic test results with phenotypes for making a final diagnosis.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Genetics & Heredity
Namshin Kim, Kyoung Hyoun Kim, Won-Jun Lim, Jiwoong Kim, Soon Ae Kim, Hee Jeong Yoo
Summary: This study aimed to identify genetic risk factors of ASD through rare de novo variants using whole exome sequencing and genetic network analyses in Korean familial dataset. It identified 36 de novo variants potentially related to ASD, with interactions between variants commonly observed in NF-kappa B signaling pathway. The small cohort size may affect results, but the study provides insights into novel ASD genes.
Article
Genetics & Heredity
Brooke Sadler, Jackson Wilborn, Lilian Antunes, Timothy Kuensting, Andrew T. Hale, Stephen R. Gannon, Kevin McCall, Carlos Cruchaga, Matthew Harms, Norine Voisin, Alexandre Reymond, Gerarda Cappuccio, Nicola Burnetti-Pierri, Marco Tartaglia, Marcello Niceta, Chiara Leoni, Giuseppe Zampino, Allison Ashley-Koch, Aintzane Urbizu, Melanie E. Garrett, Karen Soldano, Alfons Macaya, Donald Conrad, Jennifer Strahle, Matthew B. Dobbs, Tychele N. Turner, Chevis N. Shannon, Douglas Brockmeyer, David D. Limbrick, Christina A. Gurnett, Gabe Haller
Summary: The study identified a significant enrichment of rare and de novo non-synonymous variants in chromodomain (CHD) genes among individuals with Chiari I malformation (CM1), suggesting a potential role of these genes in CM1 pathogenesis. Additionally, individuals with CM1 were found to have significantly increased head circumference, with many harboring CHD rare variants exhibiting macrocephaly.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Multidisciplinary Sciences
Ashley N. Hall, Tychele N. Turner, Christine Queitsch
Summary: The study investigated copy number variation of ribosomal RNA genes (rDNA) and found no differences in probands with autism spectrum disorder and unaffected siblings. Validation results suggest that the previously reported concerted copy number variation between 45S and 5S arrays may be due to variable data quality, and meaningful correlation between 45S and 5S copy numbers was not detected in various datasets.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Peter Ebert, Peter A. Audano, Qihui Zhu, Bernardo Rodriguez-Martin, David Porubsky, Marc Jan Bonder, Arvis Sulovari, Jana Ebler, Weichen Zhou, Rebecca Serra Mari, Feyza Yilmaz, Xuefang Zhao, PingHsun Hsieh, Joyce Lee, Sushant Kumar, Jiadong Lin, Tobias Rausch, Yu Chen, Jingwen Ren, Martin Santamarina, Wolfram Hops, Hufsah Ashraf, Nelson T. Chuang, Xiaofei Yang, Katherine M. Munson, Alexandra P. Lewis, Susan Fairley, Luke J. Tallon, Wayne E. Clarke, Anna O. Basile, Marta Byrska-Bishop, Andre Corvelo, Uday S. Evani, Tsung-Yu Lu, Mark J. P. Chaisson, Junjie Chen, Chong Li, Harrison Brand, Aaron M. Wenger, Maryam Ghareghani, William T. Harvey, Benjamin Raeder, Patrick Hasenfeld, Allison A. Regier, Haley J. Abel, Ira M. Hall, Paul Flicek, Oliver Stegle, Mark B. Gerstein, Jose M. C. Tubio, Zepeng Mu, Yang Li, Xinghua Shi, Alex R. Hastie, Kai Ye, Zechen Chong, Ashley D. Sanders, Michael C. Zody, Michael E. Talkowski, Ryan E. Mills, Scott E. Devine, Charles Lee, Jan O. Korbel, Tobias Marschall, Evan E. Eichler
Summary: Through the use of long-read and strand-specific sequencing technologies, this study has achieved the de novo assembly of high-quality haplotype-resolved human genomes without the need for parent-child trio data. The research identified various forms of genetic variation, including structural variants and SV hotspots, and revealed the mechanisms of SV formation while providing SV candidates for adaptive selection within the human population.
Article
Multidisciplinary Sciences
Yafei Mao, Claudia R. Catacchio, LaDeana W. Hillier, David Porubsky, Ruiyang Li, Arvis Sulovari, Jason D. Fernandes, Francesco Montinaro, David S. Gordon, Jessica M. Storer, Marina Haukness, Ian T. Fiddes, Shwetha Canchi Murali, Philip C. Dishuck, PingHsun Hsieh, William T. Harvey, Peter A. Audano, Ludovica Mercuri, Ilaria Piccolo, Francesca Antonacci, Katherine M. Munson, Alexandra P. Lewis, Carl Baker, Jason G. Underwood, Kendra Hoekzema, Tzu-Hsueh Huang, Melanie Sorensen, Jerilyn A. Walker, Jinna Hoffman, Francoise Thibaud-Nissen, Sofie R. Salama, Andy W. C. Pang, Joyce Lee, Alex R. Hastie, Benedict Paten, Mark A. Batzer, Mark Diekhans, Mario Ventura, Evan E. Eichler
Summary: The study describes a high-quality bonobo genome assembly, comparing it to other great apes and identifying fixed structural variants that distinguish bonobos from chimpanzees. The research focuses on genes that have changed, been lost, or expanded during bonobo evolution, providing insights into incomplete lineage sorting and showing significant amino acid replacement in clustered gene segments.
Editorial Material
Genetics & Heredity
Erika Ramirez, Stephanie M. Morris, Tychele N. Turner, David H. Gutmann
NEUROLOGY-GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Meredith M. Course, Arvis Sulovari, Kathryn Gudsnuk, Evan E. Eichler, Paul N. Valdmanis
Summary: The study identified 467 human-specific expansion VNTRs that are structurally organized with repeated motifs and affected by frequent deletion and duplication events. While most VNTRs maintain stable length across superpopulations, there are exceptions with significant differences in repeat composition and length between certain VNTRs. The findings suggest that repeat motif variability, composition, and length are crucial factors to consider when characterizing VNTRs and their impact on genomic variation.
Article
Multidisciplinary Sciences
Lila Mouakkad-Montoya, Michael M. Murata, Arvis Sulovari, Ryusuke Suzuki, Beth Osia, Anna Malkova, Makoto Katsumata, Armando E. Giuliano, Evan E. Eichler, Hisashi Tanaka
Summary: eccDNA originates from linear chromosomal DNA and has been largely studied using in vitro-amplified DNA. This study isolated naive small circular DNA (nscDNA) without in vitro amplification and found that nscDNA, enriched from multicopy genomic regions including segmental duplications, may play a role in genome diversity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Genetics & Heredity
Elvisa Mehinovic, Teddi Gray, Meghan Campbell, Jenny Ekholm, Aaron Wenger, William Rowell, Ari Grudo, Jane Grimwood, Jonas Korlach, Christina Gurnett, John N. Constantino, Tychele N. Turner
Summary: This study utilized highly accurate long-read sequencing technology to identify relevant variants in a family with autism. The discovery of the de novo missense variant in the KCNC2 gene sheds light on the genetic basis of the disorder and has potential implications for future clinical applications.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Multidisciplinary Sciences
Mitchell R. Vollger, Xavi Guitart, Philip C. Dishuck, Ludovica Mercuri, William T. Harvey, Ariel Gershman, Mark Diekhans, Arvis Sulovari, Katherine M. Munson, Alexandra P. Lewis, Kendra Hoekzema, David Porubsky, Ruiyang Li, Sergey Nurk, Sergey Koren, Karen H. Miga, Adam M. Phillippy, Winston Timp, Mario Ventura, Evan E. Eichler
Summary: This study presents a comprehensive view of human segmental duplication (SD) organization using a complete human genome dataset. SDs are an important component of the genome, accounting for one-third of the total sequence, and they exhibit evolutionary differences and structural diversity between humans and other primates.
Article
Genetics & Heredity
Tristan J. Hayeck, Nicholas Stong, Evan Baugh, Ryan Dhindsa, Tychele N. Turner, Ayan Malakar, Timothy L. Mosbruger, Grace Tzun-Wen Shaw, Yuncheng Duan, Iuliana Ionita-Laza, David Goldstein, Andrew S. Allen
Summary: This study focuses on genomic regions under purifying selection that are more likely to carry disease-causing mutations. It demonstrates the importance of incorporating ancestry in intolerance estimation for accurate variant classification. The provided genome-wide intolerance map is valuable for variant prioritization.
Review
Neurosciences
Joseph D. Dougherty, Natasha Marrus, Susan E. Maloney, Benjamin Yip, Sven Sandin, Tychele N. Turner, Din Selmanovic, Kristen L. Kroll, David H. Gutmann, John N. Constantino, Lauren A. Weiss
Summary: Male sex is a strong risk factor for autism spectrum disorder (ASD), but the theory of a female protective effect (FPE) is not supported by current data.
Article
Genetics & Heredity
Jeffrey K. Ng, Pankaj Vats, Elyn Fritz-Waters, Stephanie Sarkar, Eleanor I. Sams, Evin M. Padhi, Zachary L. Payne, Shawn Leonard, Marc A. West, Chandler Prince, Lee Trani, Marshall Jansen, George Vacek, Mehrzad Samadi, Timothy T. Harkins, Craig Pohl, Tychele N. Turner
Summary: In this study, a graphics processing units-based workflow was developed to accelerate the detection of de novo variants (DNVs). The workflow was applied to whole-genome sequencing data from different sources, revealing unexpected results in the DNV callsets and potential cell line artifacts. Additionally, mutation signature analysis identified associations with B-cell lymphoma and variants in DNA repair genes. These findings have important implications for reference building and disease-related projects.
Article
Genetics & Heredity
Xueya Zhou, Pamela Feliciano, Chang Shu, Tianyun Wang, Irina Astrovskaya, Jacob B. Hall, Joseph U. Obiajulu, Jessica R. Wright, Shwetha C. Murali, Simon Xuming Xu, Leo Brueggeman, Taylor R. Thomas, Olena Marchenko, Christopher Fleisch, Sarah D. Barns, LeeAnne Green Snyder, Bing Han, Timothy S. Chang, Tychele N. Turner, William T. Harvey, Andrew Nishida, Brian J. O'Roak, Daniel H. Geschwind, Jacob J. Michaelson, Natalia Volfovsky, Evan E. Eichler, Yufeng Shen, Wendy K. Chung
Summary: In a comprehensive analysis of autism cases, we identified 60 genes, including five new risk genes, that are significantly associated with autism risk. The NAV3 gene is primarily associated with autism risk through rare inherited variants and has a moderate effect. Autistic individuals with moderate-risk genes show less cognitive impairment compared to those with highly penetrant genes.
Article
Biochemistry & Molecular Biology
Zachary L. Payne, Gervette M. Penny, Tychele N. Turner, Susan K. Dutcher
Summary: By combining PacBio HiFi and Oxford Nanopore long-read technologies, a highly accurate de novo genome assembly for Chlamydomonas reinhardtii strain CC-5816 was generated. This assembly provides important resources for further research.
PLANT COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Eleanor Sams, Jeffrey K. Ng, Victoria Tate, Ying-Chen Claire Hou, Yang Cao, Lucinda Antonacci-Fulton, Khadija Belhassan, Julie Neidich, Robi D. Mitra, F. Sessions Cole, Patricia Dickson, Jeffrey Milbrandt, Tychele N. Turner
Summary: Despite previous studies on 9p deletion and duplication syndromes, the comprehensive understanding of the genotypic and phenotypic characteristics has been limited due to small sample sizes and lack of high-resolution data. In this study, genetic data from 719 individuals worldwide were examined, revealing that most breakpoints occur in bands 9p22 and 9p24. The most common phenotype is developmental delay, and multiple neurodevelopmental disorder genes were identified in 9p22 and 9p24. Secondary structural variants related to 9p were also found, with a gender bias towards females.
HUMAN GENETICS AND GENOMICS ADVANCES
(2022)