Article
Biotechnology & Applied Microbiology
Chunli Wang, Wei Zhou, Luyan Zhang, Luhan Fu, Wei Shi, Yan Qing, Fen Lu, Jian Tang, Xiucheng Gao, Aihua Zhang, Zhanjun Jia, Yue Zhang, Xiaoke Zhao, Bixia Zheng
Summary: By performing whole exome sequencing on an unselected Chinese cohort of patients with microcephaly, we identified causative sequence variants in 65 families and discovered 8 potential novel candidate genes related to neurodevelopmental disorders/microcephaly. These results expand the morbid genome of monogenic neurodevelopmental disorders and support the adoption of whole exome sequencing as a first-tier test for individuals with microcephaly.
Article
Neurosciences
Meixin Hu, Huiping Li, Zhuxi Huang, Dongyun Li, Ying Xu, Qiong Xu, Bo Chen, Yi Wang, Jingxin Deng, Ming Zhu, Weijun Feng, Xiu Xu
Summary: Mutations in the STAMBP gene are associated with global developmental delay, microcephaly, and capillary malformation, but the functional and phenotypic characteristics of these mutations require further elucidation. A novel pathogenic mutation in STAMBP was identified in this study, which impairs the proliferation of neural stem cells and leads to microcephaly.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Genetics & Heredity
Eliane Beauregard-Lacroix, Guillermo Pacheco-Cuellar, Norbert F. Ajeawung, Jessica Tardif, Klaus Dieterich, Tabib Dabir, Dina Vind-Kezunovic, Susan M. White, Denes Zadori, Claudia Castiglioni, Lisbeth Tranebjaerg, Pernille Mathiesen Torring, Ed Blair, Marzena Wisniewska, Maria Vittoria Camurri, Yolande van Bever, Sirinart Molidperee, Juliet Taylor, Alexandre Dionne-Laporte, Sanjay M. Sisodiya, Raoul C. M. Hennekam, Philippe M. Campeau
Summary: The study identified a truncating variant in ATP6V1B2 in individuals with DOORS syndrome lacking TBC1D24 variants, suggesting ATP6V1B2 as a potential causal gene for DOORS syndrome. This finding expands the phenotype associated with ATP6V1B2 and indicates that DDOD and DOORS syndromes may be part of a spectrum of clinically and molecularly related conditions.
GENETICS IN MEDICINE
(2021)
Article
Genetics & Heredity
Guilan Xie, Yan Zhang, Wenfang Yang, Liren Yang, Ruiqi Wang, Mengmeng Xu, Landi Sun, Boxing Zhang, Xiaoyi Cui
Summary: This study identified a novel CASK gene mutation in a Chinese patient with MICPCH, broadening the mutation spectrum of this gene and providing valuable information for precise prenatal diagnosis and genetic counseling.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Jiwon Lee, Jong Eun Park, Chung Lee, Ah Reum Kim, Byung Joon Kim, Woong-Yang Park, Chang-Seok Ki, Jeehun Lee
Summary: Microcephaly is a common phenotype in patients with neurodevelopmental problems, often with genetic causes. A study conducted in Korean patients with microcephaly found a different genetic spectrum compared to other ethnicities. Whole exome sequencing (WES) along with copy number variation (CNV) analysis proved to be an effective approach for diagnosing the underlying causes of microcephaly, with a diagnostic yield of 47.5%.
FRONTIERS IN GENETICS
(2021)
Article
Oncology
Zhenxing Liu, Kaikai Guo, Xuebin Hu, Xianqin Zhang
Summary: In this study, a novel heterozygous mutation (c.1159C>T, p.Q387X) in the KRIT1 gene was identified in a four-generation family with cerebral cavernous malformation (CCM). This mutation resulted in premature termination of the KRIT1 protein, providing further evidence that KRIT1 mutations are a cause of CCM. These findings are important for the treatment and genetic diagnosis of CCM.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yu-Wen Cheng, Chia-Tung Wu, Chi-Jen Chang, Yung-Hsin Yeh, Gwo-Jyh Chang, Hsin-Yi Tsai, Lung-An Hsu
Summary: Through whole-exome sequencing, we identified a novel AGCGACAC deletion (S981fs) in the hERG gene of an LQT2 patient. Functional expression of the mutant K channel was restored by lowering temperature and using potassium channel inhibitors or openers. Our study reveals the mechanisms underlying LQT2 and offers potential therapeutic avenues.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Emanuela Salzano, Marcello Niceta, Simone Pizzi, Francesca Clementina Radio, Martina Buse, Francesca Mercadante, Sabina Barresi, Arturo Ferrara, Cecilia Mancini, Marco Tartaglia, Maria Piccione
Summary: Biallelic loss-of-function variants in MED23 can cause a recessive syndromic intellectual disability condition with or without epilepsy (MRT18). The clinical phenotype of the disorder has not been fully described yet due to the small number of reported individuals, and the spectrum and frequency of neurologic features have not been fully characterized. This study reports a 5-year-old girl with compound heterozygous for two additional MED23 variants, who exhibits global developmental delay, axial hypotonia, peripheral increased muscular tone, absent speech, generalized tonic seizures, and postnatal progressive microcephaly.
FRONTIERS IN NEUROLOGY
(2023)
Article
Medicine, General & Internal
Han Na Jang, Taeho Kim, Ah Young Jung, Beom Hee Lee, Mi-Sun Yum, Tae-Sung Ko
Summary: FOXG1 syndrome, caused by mutations in the FOXG1 gene, is associated with developmental encephalopathy and presents with infantile hypotonia and microcephaly. The diverse clinical manifestations of patients with FOXG1 mutations suggest a phenotype-genotype correlation, with brain MRI findings playing a crucial role in diagnosis.
Article
Neurosciences
Cong Zhou, Hongmei Zhu, Qinqin Xiang, Jingqun Mai, Xihan Wang, Jing Wang, Shanling Liu
Summary: This study aimed to identify pathogenic variants in a Chinese girl with developmental delay, impaired social interaction, and autistic behavior. Whole-exome sequencing revealed a pathogenic variant in the DYRK1A gene, providing important information for molecular diagnosis.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Medical Laboratory Technology
Ming Shen, Guangming Yang, Zhehui Chen, Kai Yang, Hui Dong, Chengliang Yin, Yuxuan Cheng, Chunyan Zhang, Fangyan Gu, Yanling Yang, Yaping Tian
Summary: This study identified several genetic variants in pediatric patients with developmental delay, confirming their diagnosis of cerebral creatine deficiency syndromes (CCDS). The findings expanded the knowledge of mutation spectrum in CCDS disorders and provided evidence for genetic counseling to affected families.
CLINICA CHIMICA ACTA
(2022)
Article
Genetics & Heredity
Estephania Candelo, Ana Maria Sanz, Diana Ramirez-Montano, Lorena Diaz-Ordonez, Ana Maria Granados, Fernando Rosso, Julian Nevado, Pablo Lapunzina, Harry Pachajoa
Summary: This study reports a case of vertically transmitted ZIKV infection in a 28-year-old Colombian woman with multiple fetal abnormalities, including microcephaly. Whole-exome sequencing revealed two novel heterozygous nonsense mutations in the CDK5RAP2 gene associated with ZIKV congenital syndrome, indicating a neurological syndrome. The CDK5RAP2 gene plays a role in microtubule nucleation and centriole attachment, and mutations in this gene have been linked to primary microcephaly.
FRONTIERS IN GENETICS
(2021)
Article
Pediatrics
Niaz Muhammad Khan, Basharat Hussain, Chenqing Zheng, Ayaz Khan, Muhammad Shareef Masoud, Qingquan Gu, Linhui Qiu, Naveed Altaf Malik, Muhammad Qasim, Muhammad Tariq, Junlei Chang
Summary: Microcephaly (MCPH) is a genetically heterogeneous disorder with 25 associated genes, and MCPH5 is the most frequently reported type. A study in the Pakistani population identified multiple gene variants linked to MCPH and confirmed the significant impact of three known mutations in the ASPM gene.
FRONTIERS IN PEDIATRICS
(2021)
Article
Genetics & Heredity
Julianne K. Postma, Jessica L. Zambonin, Ebtissal Khouj, Suad Alyamani, John M. Graham, Fowzan S. Alkuraya, Stephen Kundell, Melissa T. Carter
Summary: MIC-CAP is a rare genetic disorder characterized by microcephaly, capillary malformations, seizures, neurologic impairment, and developmental delay. This report provides follow-up on six patients, highlighting the variability in clinical spectrum and medical complications.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Neurosciences
Liangqun Xie, Jingrui Huang, Lei Dai, Jiefeng Luo, Jiejie Zhang, Qiaozhen Peng, Jingchi Sun, Weishe Zhang
Summary: TUBA1A mutations lead to a wide spectrum of brain abnormalities, with many more mutations likely to be unidentified. This study identified a novel TUBA1A mutation and showed that it disrupts lateral interactions between microtubules, resulting in decreased re-integration rate. Functional verification revealed the importance of TUBA1A in early neurogenesis and brain malformations related to its mutations.
MOLECULAR NEUROBIOLOGY
(2021)
Review
Neurosciences
Hamid Ullah, Abrar Hussain, Muhammad Asif, Faheem Nawaz, Mahmood Rasool
Summary: This review focuses on the role and application of natural products in the treatment of dementia and related diseases. Some synthetic/semisynthetic drugs have been proven effective in targeting dementia, while only a few natural products have been approved as drugs. However, research on bioassay-guided drug development shows the potential of natural products as drugs against dementia and related diseases.
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
(2023)
Article
Pediatrics
Amy Pan, Sierra Scodellaro, Tayyaba Khan, Inna Ushcatz, Wendy Wu, Meredith Curtis, Eyal Cohen, Ronald D. Cohn, Robin Z. Hayeems, M. Stephen Meyn, Julia Orkin, Jaskiran Otal, Miriam S. Reuter, Susan Walker, Stephen W. Scherer, Christian R. Marshall, Iris Cohn, Gregory Costain
Summary: Genome-wide sequencing can provide clinically relevant pharmacogenetic information for children with medical complexity, enabling precision prescribing practices throughout their lifelong care.
PEDIATRIC RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Zain Awamleh, Sanaa Choufani, Cheryl Cytrynbaum, Fowzan S. Alkuraya, Stephen Scherer, Sofia Fernandes, Catarina Rosas, Pedro Louro, Patricia Dias, Mariana Tomasio Neves, Sergio B. Sousa, Rosanna Weksberg
Summary: Pathogenic variants in ANKRD11 or microdeletions at 16q24.3 cause KBG syndrome and are associated with unique DNAm signatures. These DNAm profiles can be used for diagnostic purposes and can help classify individuals with variants of uncertain significance in ANKRD11.
HUMAN MOLECULAR GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Brianna K. Unda, Leon Chalil, Sehyoun Yoon, Savannah Kilpatrick, Courtney Irwin, Sansi Xing, Nadeem Murtaza, Anran Cheng, Chad Brown, Alexandria Afonso, Elizabeth McCready, Gabriel M. Ronen, Jennifer Howe, Aurelie Caye-Eude, Alain Verloes, Brad W. Doble, Laurence Faivre, Antonio Vitobello, Stephen W. Scherer, Yu Lu, Peter Penzes, Karun K. Singh
Summary: Copy number variations (CNVs) are associated with psychiatric and neurodevelopmental disorders (NDDs), and the underlying disease mechanisms for most CNVs are unknown. In this study, a 15q13.3 microdeletion mouse model and patient iPSC-derived neurons were used to investigate the developmental defects caused by the CNV. By targeting the 15q13.3 CNV genetic driver OTUD7A, the study revealed a critical OTUD7A-Ankyrin pathway in neuronal development and dysfunction in the 15q13.3 microdeletion syndrome.
MOLECULAR PSYCHIATRY
(2023)
Article
Psychiatry
Nathan A. Kimbrel, Allison E. Ashley-Koch, Xue J. Qin, Jennifer H. Lindquist, Melanie E. Garrett, Michelle F. Dennis, Lauren P. Hair, Jennifer E. Huffman, Daniel A. Jacobson, Ravi K. Madduri, Jodie A. Trafton, Hilary Coon, Anna R. Docherty, Niamh Mullins, Douglas M. Ruderfer, Philip D. Harvey, Benjamin H. McMahon, David W. Oslin, Jean C. Beckham, Elizabeth R. Hauser, Michael A. Hauser
Summary: This study aimed to identify the genetic basis of suicidal thoughts and behaviors. Through genome-wide association analysis, several risk loci for suicide were identified, and some of these loci were replicated in independent samples, providing evidence for their involvement in suicide.
Article
Oncology
Anita Villani, Scott Davidson, Nisha Kanwar, Winnie W. W. Lo, Yisu Li, Sarah Cohen-Gogo, Fabio Fuligni, Lisa-Monique Edward, Nicholas Light, Mehdi Layeghifard, Ricardo Harripaul, Larissa Waldman, Bailey Gallinger, Federico Comitani, Ledia Brunga, Reid Hayes, Nathaniel D. D. Anderson, Arun K. K. Ramani, Kyoko E. E. Yuki, Sasha Blay, Brittney Johnstone, Cara Inglese, Rawan Hammad, Catherine Goudie, Andrew Shuen, Jonathan D. D. Wasserman, Rosemarie E. E. Venier, Marianne Eliou, Miranda Lorenti, Carol Ann Ryan, Michael Braga, Meagan Gloven-Brown, Jianan A. Han, Maria Montero, Famida Spatare, James A. A. Whitlock, Stephen W. W. Scherer, Kathy Chun, Martin J. J. Somerville, Cynthia Hawkins, Mohamed Abdelhaleem, Vijay Ramaswamy, Gino R. R. Somers, Lianna Kyriakopoulou, Johann Hitzler, Mary Shago, Daniel A. A. Morgenstern, Uri Tabori, Stephen Meyn, Meredith S. S. Irwin, David Malkin, Adam Shlien
Summary: We conducted integrative somatic-germline analyses on 300 cancer patients, sequencing 864 cancer-associated genes, complete genomes, and transcriptomes. Clinically actionable variants were found in 56% of patients, leading to modified management in some cases. Therapeutically targetable variants, derived from both somatic and germline sources, were present in 54% of patients.
Article
Genetics & Heredity
Dmitrijs Rots, Taryn E. Jakub, Crystal Keung, Vissers E. L. M. Lisenka, Siddharth Banka, Rolph Pfundt, Bert B. A. de Vries, Richard H. van Jaarsveld, Saskia M. J. Hopman, Ellen van Binsbergen, Irene Valenzuela, Maja Hempel, Tatjana Bierhals, Fanny Kortuem, Francois Lecoquierre, Alice Goldenberg, Jens Michael Hertz, Charlotte Brasch Andersen, Maria Kibaek, Eloise J. Prijoles, Roger E. Stevenson, David B. Everman, Wesley G. Patterson, Linyan Meng, Charul Gijavanekar, Karl De Dios, Shenela Lakhani, Tess Levy, Matias Wagner, Dagmar Wieczorek, Paul J. Benke, Maria Soledad Lopez Garcia, Renee Perrier, Sergio B. Sousa, Pedro M. Almeida, Maria Jose Simoes, Bertrand Isidor, Wallid Deb, Andrew A. Schmanski, Omar Abdul-Rahman, Christophe Philippe, Ange-Line Bruel, Laurence Faivre, Antonio Vitobello, Christel Thauvin, Jeroen J. Smits, Livia Garavelli, Stefano G. Caraffi, Francesca Peluso, Laura Davis-Keppen, Dylan Platt, Erin Royer, Lisette Leeuwen, Margje Sinnema, Alexander P. A. Stegmann, Constance T. R. M. Stumpel, George E. Tiller, Danielle G. M. Bosch, Stephanus T. Potgieter, Shelagh Joss, Miranda Splitt, Simon Holden, Matina Prapa, Nicola Foulds, Sofia Douzgou, Kaija Puura, Regina Waltes, Andreas G. Chiocchetti, Christine M. Freitag, F. Kyle Satterstrom, Silvia De Rubeis, Joseph Buxbaum, Bruce D. Gelb, Aleksic Branko, Itaru Kushima, Jennifer Howe, Stephen W. Scherer, Alessia Arado, Chiara Baldo, Olivier Patat, Demeer Benedicte, Diego Lopergolo, Filippo M. Santorelli, Tobias B. Haack, Andreas Dufke, Miriam Bertrand, Ruth J. Falb, Angelika Riess, Peter Krieg, Stephanie Spranger, Maria Francesca Bedeschi, Maria Iascone, Sarah Josephi-Taylor, Tony Roscioli, Michael F. Buckley, Jan Liebelt, Aditi I. Dagli, Emmelien Aten, Anna C. E. Hurst, Alesha Hicks, Mohnish Suri, Ermal Aliu, Sunil Naik, Richard Sidlow, Juliette Coursimault, Gael Nicolas, Hanna Kuepper, Florence Petit, Veyan Ibrahim, Deniz Top, Francesca Di Cara, Raymond J. Louie, Elliot Stolerman, Han G. Brunner, Lisenka E. L. M. Vissers, Jamie M. Kramer, Tjitske Kleefstra
Summary: This study examines the clinical and molecular spectrum of individuals with KDM6B variants and challenges the accuracy of the current description of the disorder. Cognitive deficits are consistently observed, but the overall phenotype varies greatly. The study also demonstrates the disruptive effect of certain KDM6B variants on protein structure and introduces a functional testing paradigm for assessing these variants. The findings highlight the importance of international collaboration and rigorous functional analysis in diagnosing rare disorders.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Alanna Strong, Soumya Rao, Sandra von Hardenberg, Dong Li, Liza L. Cox, Paul C. Lee, Li Q. Zhang, Waheed Awotoye, Tamir Diamond, Jessica Gold, Catherine Gooch, Lord Jephthah Joojo Gowans, Hakon Hakonarson, Anne Hing, Kathleen Loomes, Nicole Martin, Mary L. Marazita, Tarja Mononen, David Piccoli, Rolph Pfundt, Salmo Raskin, Stephen W. Scherer, Nara Sobriera, Courtney Vaccaro, Xiang Wang, Deborah Watson, Rosanna Weksberg, Elizabeth Bhoj, Jeffrey C. Murray, Andrew C. Lidral, Azeez Butali, Michael F. Buckley, Tony Roscioli, David A. Koolen, Laurie H. Seaver, Cynthia A. Prows, Rolf W. Stottmann, Timothy C. Cox
Summary: AMOTL1 encodes angiomotin-like protein 1, a protein that regulates cell polarity, adhesion, and migration. Variants in AMOTL1 are associated with orofacial clefting, congenital heart disease, tall stature, auricular anomalies, and gastrointestinal manifestations. The study suggests that missense variants in AMOTL1, particularly in the region affecting amino acids 157-161, define a new orofacial clefting syndrome and highlight the importance of this region in its function.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Biochemistry & Molecular Biology
Claudia I. Samogy Costa, Gabriele da Silva Campos, Eduarda Morgana da Silva Montenegro, Jaqueline Yu Ting Wang, Marilia Scliar, Frederico Monfardini, Elaine Cristina Zachi, Naila C. V. Lourenco, Ada J. S. Chan, Sergio L. Pereira, Worrawat Engchuan, Bhooma Thiruvahindrapuram, Mehdi Zarrei, Stephen W. Scherer, Maria Rita Passos-Bueno
Summary: De novo variants (DNVs) analysis has been shown to be a powerful method for gene discovery in Autism Spectrum Disorder (ASD), but it has not been proven in a Brazilian ASD cohort. This study aimed to investigate the relevance of de novo and inherited variants through three-generation analysis of DNVs. Whole-exome sequencing was performed on 33 septet families, and the DNV rates (DNVr) were compared between generations and control cohorts. The results showed a marginally higher DNVr in probands compared to parents and controls, and most DNVs were found to have paternal origin in both generations. Additionally, several DNVs in parents were identified as ASD candidate genes. These findings further highlight the importance of DNVs in ASD.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Pharmacology & Pharmacy
Luciana Bertholim-Nasciben, Marilia O. Scliar, Guilherme Debortoli, Bhooma Thiruvahindrapuram, Stephen W. Scherer, Yeda A. O. Duarte, Mayana Zatz, Guilherme Suarez-Kurtz, Esteban J. Parra, Michel S. Naslavsky
Summary: This study evaluated the frequency of pharmacogenomics markers in the Brazilian population using whole-genome sequencing. The findings showed that some variants may lead to high-risk gene-drug interactions. The study concluded that next-generation sequencing for pharmacogenomics testing is feasible in the Brazilian population.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Genetics & Heredity
S. Yoo, E. Garg, L. T. Elliott, R. J. Hung, A. R. Halevy, J. D. Brooks, S. B. Bull, F. Gagnon, C. M. T. Greenwood, J. F. Lawless, A. D. Paterson, L. Sun, M. H. Zawati, J. Lerner-Ellis, R. J. S. Abraham, I Birol, G. Bourque, J-m Garant, C. Gosselin, J. Li, J. Whitney, B. Thiruvahindrapuram, J-a Herbrick, M. Lorenti, M. S. Reuter, O. O. Adeoye, S. Liu, U. Allen, F. P. Bernier, C. M. Biggs, A. M. Cheung, J. Cowan, M. Herridge, D. M. Maslove, B. P. Modi, V Mooser, S. K. Morris, M. Ostrowski, R. S. Parekh, G. Pfeffer, O. Suchowersky, J. Taher, J. Upton, R. L. Warren, R. S. M. Yeung, N. Aziz, S. E. Turvey, B. M. Knoppers, M. Lathrop, S. J. M. Jones, S. W. Scherer, L. J. Strug
Summary: HostSeq was launched in April 2020 to integrate whole genome sequencing data and clinical information of 10,000 Canadians infected with SARS-CoV-2. It aims to support research communities in understanding disease risk factors and developing interventions. HostSeq is a collaboration among 13 epidemiological studies across five provinces in Canada, providing aggregated data through two portals and individual-level data for global health research.
Article
Behavioral Sciences
Danielle A. Baribeau, Jasleen Arneja, Xuesong Wang, Jennifer Howe, John R. McLaughlin, Karen Tu, Jun Guan, Alana Iaboni, Elizabeth Kelley, Muhammad Ayub, Robert Nicolson, Stelios Georgiades, Stephen W. Scherer, Susan E. Bronskill, Evdokia Anagnostou, Jennifer D. Brooks
Summary: This study aimed to determine whether carrying an autism-associated rare genetic variant is associated with differences in health system utilization by autistic children and youth. The study found that participants with a rare variant impacting an autism-associated gene were less likely to have received psychiatric care, but there were no differences in health care costs and the proportion with complex chronic medical conditions.
Article
Biochemistry & Molecular Biology
Henry Oppermann, Elia Marcos-Graneda, Linnea A. Weiss, Christina A. Gurnett, Anne Marie Jelsig, Susanne H. Vineke, Bertrand Isidor, Sandra Mercier, Kari Magnussen, Pia Zacher, Mona Hashim, Alistair T. Pagnamenta, Simone Race, Siddharth Srivastava, Zoe Frazier, Robert Maiwald, Matthias Pergande, Donatella Milani, Martina Rinelli, Jonathan Levy, Ilona Krey, Paolo Fontana, Fortunato Lonardo, Stephanie Riley, Jasmine Kretzer, Julia Rankin, Linda M. Reis, Elena V. Semina, Miriam S. Reuter, Stephen W. Scherer, Maria Iascone, Denisa Weis, Christina R. Fagerberg, Charlotte Brasch-Andersen, Lars Kjaersgaard Hansen, Alma Kuechler, Nathan Noble, Alice Gardham, Jessica Tenney, Geetanjali Rathore, Stefanie Beck-Woedl, Tobias B. Haack, Despoina C. Pavlidou, Isis Atallah, Julia Vodopiutz, Andreas R. Janecke, Tzung-Chien Hsieh, Hellen Lesmann, Hannah Klinkhammer, Peter M. Krawitz, Johannes R. Lemke, Rami Abou Jamra, Marta Nieto, Zeynep Tumer, Konrad Platzer
Summary: This study describes the clinical presentation in an extended cohort and investigates the molecular mechanism in a Cux1(+/-) mouse model. Disease-causing CUX1 variants result in a non-syndromic phenotype of developmental delay and intellectual disability. In some individuals, this phenotype improves with age, resulting in a clinical catch-up and normal IQ in adulthood.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Mona Abdi, Elbay Aliyev, Brett Trost, Muhammad Kohailan, Waleed Aamer, Najeeb Syed, Rulan Shaath, Geethanjali Devadoss Gandhi, Worrawat Engchuan, Jennifer Howe, Bhooma Thiruvahindrapuram, Melissa Geng, Joe Whitney, Amira Syed, Jyothi Lakshmi, Sura Hussein, Najwa Albashir, Amal Hussein, Ilaria Poggiolini, Saba F. Elhag, Sasirekha Palaniswamy, Marios Kambouris, Maria de Fatima Janjua, Mohamed O. El Tahir, Ahsan Nazeer, Durre Shahwar, Muhammad Waqar Azeem, Younes Mokrab, Nazim Abdel Aati, Ammira Akil, Stephen W. Scherer, Madeeha Kamal, Khalid A. Fakhro
Summary: This study identified potentially pathogenic variants in ASD families in Qatar, with a significant proportion being single-gene variants. It also highlighted the impact of recessive variation on the ASD architecture in consanguineous settings, providing a unique genomic resource for future ASD research in the global community.
Article
Biology
Miriam S. Reuter, Dustin J. Sokolowski, J. Javier Diaz-Mejia, Johannes Keunen, Barbra de Vrijer, Cadia Chan, Liangxi Wang, Greg Ryan, David A. Chiasson, Troy Ketela, Stephen W. Scherer, Michael D. Wilson, Edgar Jaeggi, Rajiv R. Chaturvedi
Summary: Low blood flow through the fetal left heart can lead to hypoplastic left heart syndrome (HLHS). In this study, mid-gestation fetal lambs were used to create left ventricular inflow obstruction (LVIO) to investigate the effects of decreased left heart flow. The results showed that significant LVIO led to clinical features similar to HLHS, including decreased aortic valve flow, retrograde perfusion, severe left heart hypoplasia, and changes in cellular composition and gene expression consistent with fibrosis and abnormal mesenchymal programs.
COMMUNICATIONS BIOLOGY
(2023)
