Article
Multidisciplinary Sciences
Jun Li, Xiaoxuan Sun, Yang You, Qiongwei Li, Chengwen Wei, Linnan Zhao, Mengwen Sun, Hu Meng, Tian Zhang, Weihua Yue, Lifang Wang, Dai Zhang
Summary: The involvement of the high-susceptibility gene AUTS2 in social recognition deficit related to autism spectrum disorders (ASDs) is determined. It is found that deletion of AUTS2 leads to postnatal dentate gyrus development impairment and affects the Supramammillary nucleus-Dentate Gyrus-CA3 (SuM-DG-CA3) neural circuit, resulting in social recognition deficit. Additionally, a previously unknown mechanism of neural cell migration in postnatal dentate gyrus development, related to Auts2 signaling as a transcription repressor, is identified. The correction of the DG-CA3 synaptic transmission or activation of the SuM-DG circuit restores the social recognition deficit in Auts2-deleted mice.
Article
Genetics & Heredity
Xin Bi, Maureen S. Mulhern, Erica Spiegel, Ronald J. Wapner, Brynn Levy, Jennifer M. Bain, Jun Liao
Summary: This study describes a patient with developmental delays and brain abnormalities, and identifies a rare constitutional deletion of the chromosome 1q42.11 region. The study provides new insights into the clinical phenotype associated with this deletion and supports the importance of the FBXO28 gene.
Article
Genetics & Heredity
Liang-Liang Fan, Yue Sheng, Chen-Yu Wang, Ya-Li Li, Ji-Shi Liu
Summary: 7q terminal deletion syndrome is a rare condition characterized by multiple congenital malformations such as abnormal brain and facial structures, developmental delay, and intellectual disability. A rare case of a Chinese patient with this syndrome was identified, presenting with both brain structure abnormalities and cerebellar sulcus widening.
FRONTIERS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Nuria Bosch-Guiteras, Tina Uroda, Hugo A. Guillen-Ramirez, Rahel Riedo, Amiq Gazdhar, Roberta Esposito, Carlos Pulido-Quetglas, Yitzhak Zimmer, Michaela Medova, Rory Johnson
Summary: Research shows that delaying NHEJ relative to DSB formation is a simple and effective means of enhancing the efficiency and accuracy of CRISPR-deletion, improving the success rate of DNA deletion.
Article
Genetics & Heredity
Hagar Mor-Shaked, Somaya Salah, Shira Yanovsky-Dagan, Vardiella Meiner, Osama M. Atawneh, Bassam Abu-Libdeh, Orly Elpeleg, Tamar Harel
Summary: Calpainopathies are a group of disorders caused by deficiencies in calpains, which are calcium-specific proteases that modulate substrates through limited proteolysis. The clinical manifestations depend on tissue-specific expression of the defective calpain and substrate specificity. This study expands the phenotypic spectrum associated with CAPN15 variants and suggests that complete loss-of-function is associated with a recognizable syndrome of congenital malformations and developmental delay.
Article
Clinical Neurology
Linyan Meng, Pirjo Isohanni, Yunru Shao, Brett H. Graham, Scott E. Hickey, Stephanie Brooks, Anu Suomalainen, Pascal Joset, Katharina Steindl, Anita Rauch, Annette Hackenberg, Frances A. High, Amy Armstrong-Javors, Niccolo E. Mencacci, Paulina Gonzalez-Latapi, Walaa A. Kamel, Jasem Y. Al-Hashel, Bernabe Bustos, Alejandro Hernandez, Dimitri Krainc, Steven J. Lubbe, Hilde Van Esch, Chiara De Luca, Katleen Ballon, Claudia Ravelli, Lydie Burglen, Leila Qebibo, Daniel G. Calame, Tadahiro Mitani, Dana Marafi, Davut Pehlivan, Nebal W. Saadi, Yavuz Sahin, Reza Maroofian, Stephanie Efthymiou, Henry Houlden, Shazia Maqbool, Fatima Rahman, Shen Gu, Jennifer E. Posey, James R. Lupski, Jill Hunter, Michael F. Wangler, Christopher J. Carroll, Yaping Yang
Summary: This study identified a novel neurodevelopmental syndrome characterized by highly homogeneous patient phenotypes including intellectual disability, movement disorders, and cerebellar hypoplasia. The identification of multiple patients with biallelic MED27 variants supports the critical role of MED27 in normal human neural development.
ANNALS OF NEUROLOGY
(2021)
Review
Genetics & Heredity
Cecile Mejecase, Chandni Nigam, Mariya Moosajee, John C. Bladen
Summary: Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is a craniofacial disorder caused by heterozygous variants of the FOXL2 gene. It can present as two phenotypic subtypes, with type I associated with premature ovarian failure (POF) and type II having no systemic features. A mutational hotspot has been identified in the poly-alanine domain, but the BPES subtype cannot be genetically determined, requiring careful discussion of family planning advice.
Article
Medicine, General & Internal
Noemi Falcone, Annaluisa Ranieri, Andrea Vitale, Lucio Pastore, Barbara Lombardo
Summary: Psychomotor developmental delay is a common disorder in children, and early diagnosis and improved quality of life can be achieved through neuropsychomotor evaluation and the use of new technologies.
MEDICINA-LITHUANIA
(2022)
Article
Pediatrics
Ling-Yi Lin, Wen-Hao Yu, Wei-Pin Lin, Chih-Chia Chen, Yi-Fang Tu
Summary: This study investigated the agreement between caregivers' awareness of children's developmental problems and professional identification. The findings showed low agreement between caregivers' concerns and professional identification, particularly in the cognitive domain. Speech/language developmental concerns were important red-flag indicators for cognitive and emotional/behavioral developmental delays. Autism spectrum disorder and attention deficit hyperactivity disorder were significantly associated with caregivers' concerns. Child's age and mothers' level of education were also significant indicators for detecting developmental problems.
FRONTIERS IN PEDIATRICS
(2022)
Article
Genetics & Heredity
Clara Hildebrandt, Anne Fulton, Lance H. Rodan
Summary: This study describes a 15-month-old girl with a homozygous deletion in the 21q22 region, leading to the loss of multiple genes. Her symptoms include hypotonia, developmental delay, and retinopathy. The role of the absent genes in contributing to her phenotype remains unclear at this time.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Psychiatry
Ling Shan, Jun-Yan Feng, Tian-Tian Wang, Zhi-Da Xu, Fei-Yong Jia
Summary: This study investigated the prevalence and developmental profiles of Autism Spectrum Disorders (ASD) in children with Global developmental delay (GDD) from the perspective of GDD. It found that GDD children with poorer developmental levels are more likely to have comorbid ASD. The developmental profiles of GDD(+)ASD(-) children and GDD(+)ASD(+) children have common features but also differences, with the GDD(+)ASD(+) group having a lower overall development level.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Multidisciplinary Sciences
Shengfu Fan, Ying Zhang, Jiangbo Qin, Xuan Song, Meiyun Wang, Jiangping Ma
Summary: The study identified independent risk factors for DSD in children in North China, including older maternal age, introverted paternal personality, low parental education level, low family income, and rare parent-child communication. This may provide valuable insights into family risk factors for DSD.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Rachel M. Rahn, Allen Yen, Siyu Chen, Seana H. Gaines, Annie R. Bice, Lindsey M. Brier, Raylynn G. Swift, LeiLani Lee, Susan E. Maloney, Joseph P. Culver, Joseph D. Dougherty
Summary: In this study, widefield optical fluorescence imaging was used to evaluate calcium functional connectivity (FC) in the brain of the Mecp2 mutant mouse model. Results showed disrupted FC between cortical regions in Mecp2 mutant males during both juvenile development and early adulthood. Female Mecp2 mice exhibited increased contralateral FC in the motor cortex at P35, while more posterior parietal regions were implicated in adulthood. The amplitude of connection strength was increased in the male cortex, with more positive correlations and negative anticorrelations. Restoring MeCP2 protein in GABAergic neurons did not rescue these functional deficits or increase male lifespan.
Article
Biochemistry & Molecular Biology
Shun Zhang, Xiaodong Zhang, Cheng Zhang, Shanliang Xu, Danli Wang, Chunyang Guo
Summary: Pampus argenteus is an important species for commercial fishery catch and aquaculture production. The lack of pelvic fins in P. argenteus is caused by the deletion of the Hoxd9 structural domain and the absence of the Hox9 activation region in its Hoxd9b gene.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Holly C. Cappelli, Brianna D. Guarino, Anantha K. Kanugula, Ravi K. Adapala, Vidushani Perera, Matthew A. Smith, Sailaja Paruchuri, Charles K. Thodeti
Summary: TRPV4 channels regulate endothelial cell functions in the retina, with their deletion leading to increased pathological neovascularization. This suggests that TRPV4 could be a potential target for therapies against neovascular ocular diseases.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Genetics & Heredity
Nina McTiernan, Lisbeth Tranebjaerg, Anna S. Bjorheim, Jacob S. Hogue, William G. Wilson, Berkley Schmidt, Melissa M. Boerrigter, Maja L. Nybo, Marie F. Smeland, Zeynep Tumer, Thomas Arnesen
Summary: This study provides important insights into how different NAA10 missense variants impact the biochemical functions of NAA10 and explains the phenotypic variability in affected individuals.
Article
Genetics & Heredity
Smitha Kumble, Amanda M. Levy, Jaya Punetha, Hua Gao, Nicholas Ah Mew, Kwame Anyane-Yeboa, Paul J. Benke, Sara M. Berger, Lise Bjerglund, Belinda Campos-Xavier, Michael Ciliberto, Julie S. Cohen, Anne M. Comi, Cynthia Curry, Lena Damaj, Anne-Sophie Denomme-Pichon, Lisa Emrick, Laurence Faivre, Mary Beth Fasano, Alice Fievet, Richard S. Finkel, Sixto Garcia-Minaur, Amanda Gerard, Paulino Gomez-Puertas, Maria J. Guillen Sacoto, Trevor L. Hoffman, Lillian Howard, Alejandro D. Iglesias, Kosuke Izumi, Austin Larson, Anja Leiber, Reymundo Lozano, Inigo Marcos-Alcalde, Cassie S. Mintz, Sureni V. Mullegama, Rikke S. Moller, Sylvie Odent, Henry Oppermann, Elsebet Ostergaard, Marta Pacio-Miguez, Maria Palomares-Bralo, Sumit Parikh, Anna M. Paulson, Konrad Platzer, Jennifer E. Posey, Lorraine Potocki, Anya Revah-Politi, Marlene Rio, Alyssa L. Ritter, Scott Robinson, Jill A. Rosenfeld, Fernando Santos-Simarro, Sergio B. Sousa, Mathys Weber, Yili Xie, Wendy K. Chung, Natasha J. Brown, Zeynep Tumer
Summary: De novo variants in QRICH1 have been identified in individuals with intellectual disability, contributing to a neurodevelopmental disorder. The common clinical features include developmental delay, facial dysmorphism, and hypotonia, with additional findings of poor weight gain, short stature, autism spectrum disorder, seizures, and scoliosis. Some variants are inherited from mildly affected parents, suggesting variable expressivity.
Article
Psychiatry
Julie Holst Pedersen, Axel Skytthe, Jonas Bybjerg-Grauholm, Asli Sena Kucukyildiz, Liselotte Skov, Nanette Mol Debes, Zeynep Tumer
Summary: Gilles de la Tourette Syndrome (GTS) is a multifactorial neurodevelopmental disorder characterized by tics and multiple comorbidities. Twin studies indicate that both genetic and environmental risk factors are involved. The study found high concordance of GTS and chronic tic disorders in monozygotic twins, suggesting common genetic risk factors. The findings also showed higher comorbidity rates in twins with GTS or CTD compared to the general population.
JOURNAL OF PSYCHIATRIC RESEARCH
(2022)
Article
Genetics & Heredity
Maria B. Christensen, Amanda M. Levy, Nazanin A. Mohammadi, Marcello Niceta, Rauan Kaiyrzhanov, Maria Lisa Dentici, Chadi Al Alam, Viola Alesi, Valerie Benoit, Kailash P. Bhatia, Tatjana Bierhals, Christian M. Bosselmann, Julien Buratti, Bert Callewaert, Berten Ceulemans, Perrine Charles, Matthias De Wachter, Mohammadreza Dehghani, Erika D'haenens, Martine Doco-Fenzy, Michaela Gessner, Cyrielle Gobert, Ulviyya Guliyeva, Tobias B. Haack, Trine B. Hammer, Tilman Heinrich, Maja Hempel, Theresia Herget, Ute Hoffmann, Judit Horvath, Henry Houlden, Boris Keren, Christina Kresge, Candy Kumps, Damien Lederer, Alban Lermine, Francesca Magrinelli, Reza Maroofian, Mohammad Yahya Vahidi Mehrjardi, Mahdiyeh Moudi, Amelie J. Mueller, Anna J. Oostra, Beth A. Pletcher, David Ros-Pardo, Shanika Samarasekera, Marco Tartaglia, Kristof Van Schil, Julie Vogt, Evangeline Wassmer, Juliane Winkelmann, Maha S. Zaki, Michael Zech, Holger Lerche, Francesca Clementina Radio, Paulino Gomez-Puertas, Rikke S. Moller, Zeynep Tuemer
Summary: Biallelic variants of the ZNF142 gene have been associated with intellectual disability, speech impairment, seizures, and movement disorders. This study expands on previous research by providing phenotype and genotype information of 26 individuals from 16 families. The clinical features of the individuals suggest a syndromic neurodevelopmental disorder with mild to moderate intellectual disability, language and gross motor development delays, seizures, hypotonia, behavioral features, movement disorders, and facial dysmorphism.
Review
Biochemistry & Molecular Biology
Amanda M. Levy, Paulino Gomez-Puertas, Zeynep Tumer
Summary: The protein PSD-95 plays a crucial role in synaptic strength and plasticity, and its variants have been found to cause neurodevelopmental disorders. These variants may indirectly affect the interaction partners of PSD-95, leading to overlapping clinical features. This review explores the association between PSD-95 and its transmembrane interaction partners, and discusses the impact of DLG4 missense variants on protein-protein interactions and the pathogenic mechanism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Ulrik Kristoffer Stoltze, Thomas Van Overeem Hansen, Jesper Sune Brok, Karen Gronskov, Asuman Z. Turner, Lise Barlebo Ahlborn, Kjeld Schmiegelow, Karin A. W. Wadt
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Genetics & Heredity
Mathis Hildonen, Marco Ferilli, Tina Duelund Hjortshoj, Morten Duno, Lotte Risom, Mads Bak, Jakob Ek, Rikke. S. S. Moller, Andrea Ciolfi, Marco Tartaglia, Zeynep Tumer
Summary: Disease-specific DNA methylation patterns (DNAm signatures) have been established for an increasing number of genetic disorders and can be used as a valuable tool for classification of genetic variants of uncertain significance (VUS). This study demonstrates the clinical utility of a robust DNAm signature and highlights the importance of data sharing for improved diagnosis of rare genetic disorders.
Article
Medicine, General & Internal
Tanja Schlaikjaer Hartwig, Louise Ambye, Jennifer R. Gruhn, Jesper Friis Petersen, Tine Wronding, Letizia Amato, Andrew Chi-Ho Chan, Boyang Ji, Maiken Hemme Bro-Jorgensen, Lene Werge, Mette Marie Babiel Schmidt Petersen, Clara Brinkmann, Julie Birch Petersen, Morten Duno, Iben Bache, Markus J. Herrgard, Finn Stener Jorgensen, Eva R. Hoffmann, Henriette Svarre Nielsen
Summary: This study validates the feasibility of using cell-free fetal DNA (cffDNA) from maternal blood for the detection of fetal aneuploidy in cases of pregnancy loss. The results show that this method has a high sensitivity and specificity in distinguishing between euploid and aneuploid pregnancy loss, providing valuable information for clinical management.
Article
Genetics & Heredity
Victoria A. Bjerregaard, Amanda M. Levy, Mille S. Batz, Ravina Salehi, Mathis Hildonen, Trine B. Hammer, Rikke S. Moller, Claus Desler, Zeynep Tumer
Summary: FOXG1 (Forkhead box g1) syndrome is a neurodevelopmental disorder caused by a defective transcription factor, FOXG1, which is important for normal brain development and function. This study found that individuals with FOXG1 variants had decreased mitochondrial content and adenosine triphosphate (ATP) levels, as well as morphological changes in the mitochondrial network, indicating mitochondrial dysfunction as a possible factor in the pathogenesis of FOXG1 syndrome. Further research is needed to understand how FOXG1 deficiency affects mitochondrial homeostasis.
Article
Genetics & Heredity
Ulrik Kristoffer Stoltze, Mathis Hildonen, Thomas Van Overeem Hansen, Jon Foss-Skiftesvik, Anna Byrjalsen, Malene Lundsgaard, Laura Pignata, Karen Gronskov, Asuman Z. Tumer, Kjeld Schmiegelow, Jesper Sune Brok, Karin A. W. Wadt
Summary: This study found that the development of Wilms tumors is associated with genetic and epigenetic factors, with female patients more likely to carry pathogenic variants. Early detection of underlying predisposition may have important implications for diagnosis, treatment, and genetic counseling for Wilms tumors.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Psychiatry
Pritesh Jain, Tyne Miller-Fleming, Apostolia R. Topaloudi, Dongmei K. Yu, Petros Drineas, Marianthi Georgitsi, Zhiyu Yang, Renata Rizzo, Kirsten R. Mueller-Vahl, Zeynep A. Tumer, Nanette Mol Debes, Andreas S. Hartmann, Christel E. Depienne, Yulia S. Worbe, Pablo Mir, Danielle C. Cath, Dorret Boomsma, Veit Roessner, Tomasz Wolanczyk, Piotr Janik, Natalia Szejko, Cezary Zekanowski, Csaba Barta, Zsofia Nemoda, Zsanett Tarnok, Joseph D. Buxbaum, Dorothy Grice, Jeffrey Glennon, Hreinn Stefansson, Bastian Hengerer, Noa Benaroya-Milshtein, Francesco Cardona, Tammy Hedderly, Isobel Heyman, Chaim Huyser, Astrid Morer, Norbert Mueller, Alexander Munchau, Kerstin J. Plessen, Cesare Porcelli, Susanne Walitza, Anette Schrag, Davide Martino, Andrea Dietrich, Carol A. Mathews, Jeremiah M. Scharf, Pieter J. Hoekstra, Lea K. Davis, Peristera Paschou
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Genetics & Heredity
Amanda M. Levy, Mythily Ganapathi, Wendy K. K. Chung, Zeynep Tumer
Summary: The rare brain disorder DLG4-related synaptopathy is caused by de novo variants in DLG4, primarily resulting in protein-truncating changes. However, there are also DLG4 variants predicted to affect RNA splicing, and their pathogenicity remains uncertain without functional RNA studies. This study describes a case where a deep intronic DLG4 variant was identified using whole genome sequencing and subsequent functional analysis revealed alternative DLG4 transcripts that lead to protein-truncation.
Article
Medicine, General & Internal
Thomas Eggermann, David Monk, Guiomar Perez de Nanclares, Masayo Kagami, Eloise Giabicani, Andrea Riccio, Zeynep Tumer, Jennifer M. Kalish, Maithe Tauber, Jessica Duis, Rosanna Weksberg, Eamonn R. Maher, Matthias Begemann, Miriam Elbracht
Summary: This article summarizes the molecular mechanisms, diagnosis, and treatment of imprinting disorders. It also provides an overview of future research and the impact of these disorders on patient quality of life. Imprinting disorders are congenital conditions characterized by disturbances in genomic imprinting. The most common types include Prader-Willi, Angelman, and Beckwith-Wiedemann syndromes. Diagnosis is challenging due to the non-specific clinical manifestations, and treatment is currently symptomatic. Personalized therapies are being developed to address the rarity of these disorders.
NATURE REVIEWS DISEASE PRIMERS
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Thomas Eggermann, Deborah Mackay, Karen Temple, David Monk, Eamonn Maher, Andrea Riccio, Frederic Brioude, Agnes Linglart, Matthias Begemann, Katja Eggermann, Miriam Elbracht, Karen Gronskov, Jet Bliek, Paola Lombardi, Guiomar Perez de Nanclares, Masayo Kagami, Irene Netchine, Tsutomu Ogata, Zeynep Tumer
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Anne Hugon, C. Immesoete, B. Chaumette, J. Clayton-Smith, C. Cravero, S. Daugy, D. Dan, S. Douzgou Houge, L. Faivre, S. Heide, R. C. Hennekam, T. Kleefstra, L. Laporte, I. Marchetti-Waternaux, A. Manunta, G. Mosiello, S. Peudenier, V. Des Portes, M. P. Reymond, S. Selatnia, A. Sundqvist, M. Tartaglia, Z. Tumer, B. Tumiene, L. Vissers, K. Vyshka, D. Wieczorek, G. Zampino, A. Renieri, A. Verloes
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
