Article
Pediatrics
Sapna Sandal, Ishwar Chander Verma, Sunita Bijarnia Mahay, Sudhisha Dubey, R. K. Sabharwal, Samarth Kulshrestha, Renu Saxena, Praveen Suman, Praveen Kumar, Ratna Dua Puri
Summary: This study aimed to determine the diagnostic yield of next generation sequencing (NGS) in patients with unexplained intellectual disability (ID), and its impact on clinical management and genetic counseling. It found a high diagnostic yield of NGS in the study cohort, with autosomal recessive intellectual disability being the most common cause of ID. The study emphasizes the importance of phenotype in genetic testing and highlights the need for more data on the molecular genetic spectrum of ID in India.
INDIAN JOURNAL OF PEDIATRICS
(2023)
Article
Genetics & Heredity
Sebastien Kury, Jinwei Zhang, Thomas Besnard, Alfonso Caro-Llopis, Xue Zeng, Stephanie M. Robert, Sunday S. Josiah, Emre Kiziltug, Anne-Sophie Denomme-Pichon, Benjamin Cogne, Adam J. Kundishora, Le T. Hao, Hong Li, Roger E. Stevenson, Raymond J. Louie, Wallid Deb, Erin Torti, Virginie Vignard, Kirsty McWalter, F. Lucy Raymond, Farrah Rajabi, Emmanuelle Ranza, Detelina Grozeva, Stephanie A. Coury, Xavier Blanc, Elise Brischoux-Boucher, Boris Keren, Katrin Ounap, Karit Reinson, Pilvi Ilves, Ingrid M. Wentzensen, Eileen E. Barr, Solveig Heide Guihard, Perrine Charles, Eleanor G. Seaby, Kristin G. Monaghan, Marlene Rio, Yolande van Bever, Marjon van Slegtenhorst, Wendy K. Chung, Ashley Wilson, Delphine Quinquis, Flora Breheret, Kyle Retterer, Pierre Lindenbaum, Emmanuel Scalais, Lindsay Rhodes, Katrien Stouffs, Elaine M. Pereira, Sara M. Berger, Sarah S. Milla, Ankita B. Jaykumar, Melanie H. Cobb, Shreyas Panchagnula, Phan Q. Duy, Marie Vincent, Sandra Mercier, Brigitte Gilbert-Dussardier, Xavier Le Guillou, Severine Audebert-Bellanger, Sylvie Odent, Sebastien Schmitt, Pierre Boisseau, Dominique Bonneau, Annick Toutain, Estelle Colin, Laurent Pasquier, Richard Redon, Arjan Bouman, Jill A. Rosenfeld, Michael J. Friez, Helena Perez-Pena, Syed Raza Akhtar Rizvi, Shozeb Haider, Stylianos E. Antonarakis, Charles E. Schwartz, Francisco Martinez, Stephane Bezieau, Kristopher T. Kahle, Bertrand Isidor
Summary: This study identified WNK3 gene variants associated with a rare form of X-linked intellectual disability, which showed variable manifestations of epilepsy and structural brain abnormalities. The study also revealed impaired phosphorylation regulation of KCC2 as a possible mechanism underlying the disease.
GENETICS IN MEDICINE
(2022)
Article
Genetics & Heredity
Kornelia Tripolszki, Erina Sasaki, Ronja Hotakainen, Abdul Halim Kassim, Catarina Pereira, Arndt Rolfs, Peter Bauer, William Reardon, Aida M. Bertoli-Avella
Summary: In this study, researchers identified an X-linked syndrome affecting 13 male patients from a single family over three generations. The syndrome is characterized by various symptoms and is typically fatal in infancy, with female carriers being asymptomatic. Genome sequencing revealed a unique candidate variant in the OTUD5 gene, providing compelling evidence of genotype-phenotype association.
Article
Neurosciences
Mao-Qiang Tian, Xiao-Rong Liu, Si-Mei Lin, Jie Wang, Sheng Luo, Liang-Di Gao, Xiao-Bin Chen, Xiao-Yu Liang, Zhi-Gang Liu, Na He, Yong-Hong Yi, Wei-Ping Liao
Summary: Novel BRWD3 variants were identified in patients with idiopathic partial epilepsy (IPE), including two recurrent missense variants and one intronic variant close to splice site. These variants were found to be significantly associated with IPE and showed a higher frequency in patients compared to controls. Furthermore, missense variants located in specific domains of BRWD3 were associated with epilepsy, while destructive variants were associated with intellectual disability.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Review
Medicine, General & Internal
Qingyun Kang, Liming Yang, Hongmei Liao, Liwen Wu, Bo Chen, Sai Yang, Xiaojun Kuang, Haiyang Yang, Caishi Liao
Summary: This study reported a Chinese patient with a novel nonsense mutation in CNKSR2 gene, diagnosed with Houge type of X-linked syndromic mental retardation. The findings could expand the spectrum of CNKSR2 mutations and support further research on this type of disease.
Article
Genetics & Heredity
Anna Karolina Silva Ramos, Erica Carine Campos Caldas-Rosa, Barbara Merfort Ferreira, Beatriz Ribeiro Versiani, Patricia Natalia Moretti, Silviene Fabiana de Oliveira, Aline Pic-Taylor, Juliana F. Mazzeu
Summary: The ZDHHC9 gene mutation leads to intellectual disabilities and symptoms such as low IQ, developmental delay, facial dysmorphisms, and skeletal defects. Although there are differences in clinical manifestations among different patients, intellectual disabilities and developmental delay are reported in all cases. These mutations mainly occur in the arginine residues located in the cytoplasmic domains of the protein and may be hotspot mutations.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Biotechnology & Applied Microbiology
Zahra Rashvand, Kimia Kahrizi, Hossein Najmabadi, Reza Najafipour, Mir Davood Omrani
Summary: Intellectual disability (ID) is a common feature of many rare disorders, which are highly heterogeneous and complex. The study identified a novel pathogenic splicing variant c.1441-1G>A in the C12orf4 gene in two Iranian patients with non-syndromic ID, contributing to a better understanding of the genotype-phenotype correlation in this very rare disease.
JOURNAL OF GENE MEDICINE
(2022)
Article
Cell Biology
Ken Saida, Tokiko Fukuda, Daryl A. Scott, Toru Sengoku, Kazuhiro Ogata, Annarita Nicosia, Andres Hernandez-Garcia, Seema R. Lalani, Mahshid S. Azamian, Haley Streff, Pengfei Liu, Hongzheng Dai, Takeshi Mizuguchi, Satoko Miyatake, Miki Asahina, Tsutomu Ogata, Noriko Miyake, Naomichi Matsumoto
Summary: X-linked intellectual disability (XLID) is a common disorder with over 100 mutated genes reported. This study identified pathogenic OTUD5 variants in two families with developmental delay, showing features of LINKage-specific-deubiquitylation-deficiency-induced embryonic defects (LINKED) syndrome. Unlike previous reports of early lethality, the patients in this study have survived with a milder phenotype.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Pediatrics
Wen Zhang, Dong Li, Nan Pang, Li Jiang, Baomin Li, Fanghua Ye, Fang He, Shimeng Chen, Fangyun Liu, Jing Peng, Jinghua Yin, Fei Yin
Summary: This study investigated the applicability of fragile X syndrome (FXS) testing in unexplained ID/GDD individuals with negative or absent genetic testing, highlighting the utility of FXS testing in identifying the etiology of ID/GDD individuals.
FRONTIERS IN PEDIATRICS
(2022)
Article
Pediatrics
Lu Qing, Yufei Zhao, Ye Zhang, Yuanlin Guan, Guoyan Lu
Summary: This case report highlights the value of mNGS in diagnosing PCP when conventional diagnostic methods fail to identify the agent. Early onset of recurrent infectious diseases may indicate the presence of an immunodeficiency disease, for which timely genetic analysis and diagnosis are crucial.
FRONTIERS IN PEDIATRICS
(2023)
Article
Biotechnology & Applied Microbiology
Saide Betul Arslan Satilmis, Emin Emre Kurt, Ebru Perim Akcay, Ali Sazci, Ahmet Cevdet Ceylan
Summary: X-linked intellectual disability type Nascimento (XIDTN) is caused by a novel missense mutation in the UBE2A gene. Phenotypic effects were demonstrated in a large family, with intellectual disability and speech disorders being common features. The genotype-phenotype correlation and phenotypic variations in XIDTN were identified through a literature review.
JOURNAL OF GENE MEDICINE
(2021)
Article
Genetics & Heredity
Charles E. Schwartz, Raymond J. Louie, Annick Toutain, Cindy Skinner, Michael J. Friez, Roger E. Stevenson
Summary: Genes involved in transcription, mitochondrial function, glycoprotein metabolism, and ubiquitination dominate the list of 21 new genes associated with X-linked intellectual disability since 2017. Approximately 21% of named XLID syndromes and 25% of numbered nonsyndromic XLID families remain unresolved. Despite a slower pace of discovering new XLID genes in the past 5 years, the density of genes causing intellectual disability on the X chromosome is still twice that on the autosomes.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Pediatrics
Shaomin Wu, Yingchun Zheng, Cailing Xu, Jiahui Fu, Fu Xiong, Fang Yang
Summary: This study analyzed genetic mutations in a Chinese pedigree affected with Alpha-thalassemia X-linked intellectual disability syndrome, providing a precise diagnosis and genetic counseling.
FRONTIERS IN PEDIATRICS
(2022)
Article
Genetics & Heredity
Nino Spataro, Juan Pablo Trujillo-Quintero, Carmen Manso, Elisabeth Gabau, Nuria Capdevila, Victor Martinez-Glez, Antoni Berenguer-Llergo, Sara Reyes, Anna Brunet, Neus Baena, Miriam Guitart, Anna Ruiz
Summary: Neurodevelopmental disorders (NDDs) affect a significant percentage of the population, with genetic factors accounting for a large portion of cases. A gene panel including numerous genes was used to identify the genetic causes of NDDs in patients with intellectual disability (ID)/global developmental delay (GDD) and/or autism (ASD). The panel had a high diagnostic yield and revealed the genetic heterogeneity of NDDs. Different phenotypic features were observed among patients with pathogenic variants, highlighting the importance of in-depth phenotypic profiling. Whole exome-sequencing (WES) may be a more reliable solution for NDD molecular diagnosis, but the gene panel can serve as a first-tier approach in WES studies.
Article
Genetics & Heredity
Sylwia Rzonca-Niewczas, Jolanta Wierzba, Ewa Kaczorowska, Milena Poryszewska, Joanna Kosinska, Piotr Stawinski, Rafal Ploski, Jerzy Bal
Summary: Investigating a nonsense variant of the XLID gene WDR13, c.757C>T, found in males with familial intellectual disability, led to a significant decrease in WDR13 expression and dysregulation of other genes related to intellectual disability. This suggests the pathogenic nature of the detected variant and its impact on the functioning of genes essential for the nervous system, particularly synaptic plasticity.
Editorial Material
Biochemistry & Molecular Biology
Rebecca Schuele, Dagmar Timmann, Corrie E. Erasmus, Jennifer Reichbauer, Melanie Wayand, Bart van de Warrenburg, Ludger Schoels, Carlo Wilke, Andrea Bevot, Stephan Zuchner, Sergi Beltran, Steven Laurie, Leslie Matalonga, Holm Graessner, Matthis Synofzik
EUROPEAN JOURNAL OF HUMAN GENETICS
(2021)
Correction
Biochemistry & Molecular Biology
Holger Hengel, Rebecca Buchert, Marc Sturm, Tobias B. Haack, Yvonne Schelling, Muhammad Mahajnah, Rajech Sharkia, Abdussalam Azem, Ghassan Balousha, Zaid Ghanem, Mohammed Falana, Osama Balousha, Suhail Ayesh, Reinhard Keimer, Werner Deigendesch, Jimmy Zaidan, Hiyam Marzouqa, Peter Bauer, Ludger Schols
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Clinical Neurology
Allan Bayat, Guillem Valles-Ibanez, Manuela Pendziwiat, Alexej Knaus, Kerstin Alt, Elisa Biamino, Annette Bley, Sophie Calvert, Patrick Carney, Alfonso Caro-Llopis, Berten Ceulemans, Janice Cousin, Suzanne Davis, Vincent Portes, Patrick Edery, Eleina England, Carlos Ferreira, Jeremy Freeman, Blanca Gener, Magali Gorce, Delphine Heron, Michael S. Hildebrand, Aleksandra Jezela-Stanek, Pierre-Simon Jouk, Boris Keren, Katja Kloth, Gerhard Kluger, Marius Kuhn, Johannes R. Lemke, Hong Li, Francisco Martinez, Caroline Maxton, Heather C. Mefford, Giuseppe Merla, Hanna Mierzewska, Alison Muir, Sandra Monfort, Joost Nicolai, Jennifer Norman, Gina O'Grady, Barbara Oleksy, Carmen Orellana, Laura Elena Orec, Charlotte Peinhardt, Ewa Pronicka, Monica Rosello, Fernando Santos-Simarro, Eva Maria Christina Schwaibold, Alexander P. A. Stegmann, Constance T. Stumpel, Elzbieta Szczepanik, Iwona Terczynska, Julien Thevenon, Andreas Tzschach, Patrick Van Bogaert, Roberta Vittorini, Sonja Walsh, Sarah Weckhuysen, Barbara Weissman, Lynne Wolfe, Alexandre Reymond, Pasquelena De Nittis, Annapurna Poduri, Heather Olson, Pasquale Striano, Gaetan Lesca, Ingrid E. Scheffer, Rikke S. Moller, Lynette G. Sadleir
Summary: PIGN encephalopathy is a complex autosomal recessive disorder that affects epilepsy phenotypes, often accompanied by developmental impairment.
Article
Genetics & Heredity
Ruth J. Falb, Amelie J. Mueller, Wolfram Klein, Mona Grimmel, Ute Grasshoff, Stephanie Spranger, Petra Stoebe, Darja Gauck, Alma Kuechler, Nicola Dikow, Eva M. C. Schwaibold, Christoph Schmidt, Luisa Averdunk, Rebecca Buchert, Tilman Heinrich, Natalia Prodan, Joohyun Park, Martin Kehrer, Marc Sturm, Olga Kelemen, Silke Hartmann, Denise Horn, Dirk Emmerich, Nina Hirt, Armin Neumann, Glen Kristiansen, Ulrich Gembruch, Susanne Haen, Reiner Siebert, Sabine Hentze, Markus Hoopmann, Stephan Ossowski, Stephan Waldmueller, Stefanie Beck-Woedl, Dieter Glaeser, Ismail Tekesin, Felix Distelmaier, Olaf Riess, Karl-Oliver Kagan, Andreas Dufke, Tobias B. Haack
Summary: This study identified multiple disease genes associated with fetal akinesia through clinical characterization and genetic sequencing. It also revealed the association between the KIF21A gene and severe neurogenic FA sequence with arthrogryposis and muscle development disorders.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Erika Souche, Sergi Beltran, Erwin Brosens, John W. Belmont, Magdalena Fossum, Olaf Riess, Christian Gilissen, Amin Ardeshirdavani, Gunnar Houge, Marielle van Gijn, Jill Clayton-Smith, Matthis Synofzik, Nicole de Leeuw, Zandra C. Deans, Yasemin Dincer, Sebastian H. Eck, Saskia van eer Crabben, Meena Balasubramanian, Holm Graessner, Marc Sturm, Helen Firth, Alessandra Ferlini, Rima Nabbout, Elfride De Baere, Thomas Liehr, Milan Macek, Gert Matthijs, Hans Scheffer, Peter Bauer, Helger G. Yntema, Marjan M. Weiss
Summary: Guidelines for diagnostic Next Generation Sequencing (NGS) were published in 2016 to assist laboratories in implementing and accrediting NGS in a diagnostic setting. With the increasing use of Whole Genome Sequencing (WGS) in rare disease diagnosis, there was a need to re-evaluate and update the previously published guidelines. The aim of these recommendations is to provide technical advice and aid clinical decision-making for geneticists and bioinformaticians.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Genetics & Heredity
Andreas Dufke, Markus Hoopmann, Stephan Waldmuller, Natalia Carmen Prodan, Stefanie Beck-Woedl, Ute Grasshoff, Tilman Heinrich, Angelika Riess, Martin Kehrer, Ruth J. Falb, Alexandra Liebmann, Cristiana Roggia, Miriam Stampfer, Malou Schadeck, Amelie J. Mueller, Mona Grimmel, Petra Stoebe, Darja Gauck, Rebecca Buchert-Lo, Sarah Baumann, Karin Schaeferhoff, Miriam Bertrand, Benita Menden, Marc Sturm, Leon Schuetz, Olaf Riess, Stephan Ossowski, Tobias B. Haack, Karl Oliver Kagan
Summary: Trio exome sequencing has a high diagnostic yield in fetuses with multiple structural defects, identifying the genetic cause in over 40% of cases.
PRENATAL DIAGNOSIS
(2022)
Article
Clinical Neurology
Nataliya Di Donato, Renzo Guerrini, Charles J. Billington, A. James Barkovich, Philine Dinkel, Elena Freri, Michael Heide, Elliot S. Gershon, Tracy S. Gertler, Robert J. Hopkin, Suma Jacob, Sarah K. Keedy, Daniz Kooshavar, Paul J. Lockhart, Dietmar R. Lohmann, Iman G. Mahmoud, Elena Parrini, Evelin Schrock, Giulia Severi, Andrew E. Timms, Richard Webster, Mary J. H. Willis, Maha S. Zaki, Joseph G. Gleeson, Richard J. Leventer, William B. Dobyns
Summary: Reelin, encoded by the RELN gene, is critical for brain development and function. Variants in RELN have been associated with various neurodevelopmental disorders, including lissencephaly and potentially schizophrenia. This study provides data on individuals with biallelic and monoallelic RELN variants, expanding the spectrum of associated phenotypes.
Article
Clinical Neurology
Isabell Cordts, Demet Oender, Andreas Traschuetz, Xenia Kobeleva, Ivan Karin, Martina Minnerop, Peter Koertvelyessy, Saskia Biskup, Stephan Forchhammer, Johannes Binder, Andreas Tzschach, Frank Meiss, Axel Schmidt, Martina Kreiss, Kirsten Cremer, Martin A. Mensah, Joohyun Park, Maren Rautenberg, Natalie Deininger, Marc Sturm, Paul Lingor, Thomas Klopstock, Markus Weiler, Franz Marxreiter, Matthis Synofzik, Christian Posch, Judith Sirokay, Thomas Klockgether, Tobias B. Haack, Marcus Deschauer
Summary: This study investigates patients with biallelic variants in NER genes presenting predominantly with neurological signs and identifies NERDND as an underdiagnosed cause of adult-onset neurodegeneration.
MOVEMENT DISORDERS
(2022)
Article
Genetics & Heredity
Joohyun Park, Arianna Tucci, Valentina Cipriani, German Demidov, Clarissa Rocca, Jan Senderek, Michaela Butryn, Ana Velic, Tanya Lam, Evangelia Galanaki, Elisa Cali, Letizia Vestito, Reza Maroofian, Natalie Deininger, Maren Rautenberg, Jakob Admard, Gesa-Astrid Hahn, Claudius Bartels, Nienke J. H. van Os, Rita Horvath, Patrick F. Chinnery, May Yung Tiet, Channa Hewamadduma, Marios Hadjivassiliou, George K. Tofaris, Nicholas W. Wood, Stefanie N. Hayer, Friedemann Bender, Benita Menden, Isabell Cordts, Katrin Klein, Huu Phuc Nguyen, Joachim K. Krauss, Christian Blahak, Tim M. Strom, Marc Sturm, Bart van de Warrenburg, Holger Lerche, Boris Macek, Matthis Synofzik, Stephan Ossowski, Dagmar Timmann, Marc E. Wolf, Damian Smedley, Olaf Riess, Ludger Schoels, Henry Houlden, Tobias B. Haack, Holger Hengel
Summary: This study investigated heterozygous variants in the UCHL1 gene and identified a novel disease mechanism associated with ataxia. Through gene-burden analyses and proteomics, it was found that haploinsufficiency of UCHL1 can cause neurodegenerative disorders.
GENETICS IN MEDICINE
(2022)
Article
Genetics & Heredity
Lucy Loong, Agostina Tardivo, Alexej Knaus, Mona Hashim, Alistair T. Pagnamenta, Kerstin Alt, Helena Boehrer-Rabel, Alfonso Caro-Llopis, Trevor Cole, Felix Distelmaier, Patrick Edery, Carlos R. Ferreira, Aleksandra Jezela-Stanek, Bronwyn Kerr, Gerhard Kluger, Peter M. Krawitz, Marius Kuhn, Johannes R. Lemke, Gaetan Lesca, Sally Ann Lynch, Francisco Martinez, Caroline Maxton, Hanna Mierzewska, Sandra Monfort, Joost Nicolai, Carmen Orellana, Deb K. Pal, Rafal Ploski, Oliver W. Quarrell, Monica Rosello, Malgorzata Rydzanicz, Ataf Sabir, Robert Smigiel, Alexander P. A. Stegmann, Helen Stewart, Constance Stumpel, Elzbieta Szczepanik, Andreas Tzschach, Lynne Wolfe, Jenny C. Taylor, Yoshiko Murakami, Taroh Kinoshita, Allan Bayat, Usha Kini
Summary: This study analyzed 61 cases of biallelic PIGN variants and found that biallelic-truncating variants usually result in severe Fryns syndrome phenotype, while the remaining cases are associated with neurological problems. The study suggests the presence of other functionally important regions in PIGN that are yet to be discovered.
GENETICS IN MEDICINE
(2022)
Article
Clinical Neurology
Theresa Goebel, Lea Berninger, Andrea Schlump, Bernd Feige, Kimon Runge, Kathrin Nickel, Miriam A. Schiele, Ludger Tebartz van Elst, Alrun Hotz, Svenja Alter, Katharina Domschke, Andreas Tzschach, Dominique Endres
Summary: This article presents a case of Baraitser-Winter cerebrofrontofacial syndrome patient with obsessive-compulsive symptoms, confirming the association between the syndrome and OCS through various diagnostic methods, providing evidence for further research into the pathophysiology of OCD.
JOURNAL OF NEURAL TRANSMISSION
(2022)
Article
Medicine, General & Internal
Rebecca Buchert, Elisabeth Schenk, Thomas Hentrich, Nico Weber, Katharina Rall, Marc Sturm, Oliver Kohlbacher, Andre Koch, Olaf Riess, Sara Y. Brucker, Julia M. Schulze-Hentrich
Summary: By analyzing the genetic material of discordant monozygotic twins with MRKH, potential genetic causes were identified. The study revealed the involvement of estrogen in the pathology of MRKH, although no clear pathogenic differences were detected.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Clinical Neurology
Johanna Haertl, Julia Hartberger, Silke Wunderlich, Isabell Cordts, Cemsel Bafligil, Marc Sturm, Dominik Westphal, Tobias Haack, Bernhard Hemmer, Benno David Ikenberg, Marcus Deschauer
Summary: This study found that genetic variants have a crucial impact on the occurrence of ischemic stroke in young individuals. Genetic screening can help identify genetic diseases causing stroke and provide valuable information for the medical clarification of acute stroke.
JOURNAL OF NEUROLOGY
(2023)
Article
Psychiatry
Isabelle Matteit, Andrea Schlump, Marco Reisert, Katharina von Zedtwitz, Kimon Runge, Kathrin Nickel, Miriam A. Schiele, Volker A. Coenen, Katharina Domschke, Andreas Tzschach, Dominique Endres
Summary: This study investigates the occurrence of obsessive-compulsive symptoms (OCS) in patients with chromosomal disorders involving the X chromosome. Two patients with Turner syndrome and triple X syndrome were examined and both showed severe OCS. The MRI analysis revealed significant gray matter volume loss in the orbitofrontal cortex and other brain regions, suggesting an association between these chromosomal disorders and OCD pathophysiology.
WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY
(2023)