Article
Neurosciences
Marc P. Forrest, Peter Penzes
Summary: Copy number variants (CNVs) are genomic imbalances associated with neuropsychiatric disorders. Research on CNVs provides insights into polygenic disease mechanisms and offers potential therapeutic development strategies. This review outlines models for gene interactions within CNVs and explores different approaches in studying rodent and stem cell disease models. Recent work highlights the rescue of CNV-mediated pathophysiology through genetic and pharmacological strategies targeting synaptic pathways.
CURRENT OPINION IN NEUROBIOLOGY
(2023)
Article
Clinical Neurology
Rebecca J. Levy, Katherine W. Timothy, Jack F. G. Underwood, Jeremy Hall, Jonathan A. Bernstein, Sergiu P. Pasca
Summary: Mutations in CACNA1C gene can cause both central nervous system and cardiac disorders, manifesting as developmental delay, incoordination, hypotonia, autism spectrum disorder, and other neuropsychiatric symptoms. These findings suggest the crucial role of calcium channels in neural development and emphasize the importance of screening and treating these symptoms.
PEDIATRIC NEUROLOGY
(2023)
Review
Psychology, Developmental
Mark H. Johnson, Tony Charman, Andrew Pickles, Emily J. H. Jones
Summary: The AMEND framework aims to redefine the field of future research on neurodevelopmental disorders by proposing methods to separate early-stage disturbance markers from later developmental modifiers. Understanding how different perturbations and modifiers interact to produce phenotypic outcomes can advance both theoretical understanding and clinical approaches to developmental psychopathology in early childhood.
JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
(2021)
Review
Genetics & Heredity
Yulian Fang, Yaqiong Cui, Zhaoqing Yin, Mengzhu Hou, Pan Guo, Hanjie Wang, Nan Liu, Chunquan Cai, Mingbang Wang
Summary: This study conducted a systematic review and meta-analysis on the association between genetic variants and autism spectrum disorder (ASD) risk. The results revealed significant associations between certain single nucleotide polymorphisms (SNPs) of candidate genes, including CNTNAP2, MTHFR, OXTR, and VDR, and increased ASD risk.
Article
Chemistry, Medicinal
Noor B. Almandil, Abdulla AlSulaiman, Sumayh A. Aldakeel, Deem N. Alkuroud, Halah Egal Aljofi, Safah Alzahrani, Aishah Al-mana, Asma A. Alfuraih, Majed Alabdali, Fahd A. Alkhamis, Sayed AbdulAzeez, J. Francis Borgio
Summary: This study integrated transcriptome and exome genotyping data to identify functional variants associated with autism spectrum disorder and their impact on gene expression. Significant differences were found in gene expression between autistic patients and controls. In addition, the study identified important genetic variants associated with autism spectrum disorder in Arab populations.
Article
Oncology
Nafeesa Moksud, Marta Wagner, Konrad Pawelczyk, Irena Porebska, Beata Muszczynska-Bernhard, Aneta Kowal, Andrzej Wisniewski, Monika Kosacka, Julia Konczak, Pawel Karpinski, Dominik Frydryk, Anna Andrzejczak, Lidia Karabon, Piotr Kusnierczyk, Monika Jasek
Summary: This study found that single nucleotide polymorphisms (SNPs) of PDCD1, CD274, and HAVCR2 genes are associated with the risk and outcomes of non-small cell lung cancer (NSCLC) subtypes, including squamous cell lung cancer (LUSC) and lung adenocarcinoma (LUAD). Specific genotypes of rs4143815 and rs4742098 were associated with increased risk of developing LUSC. Additionally, rs4143815 was found to be an independent predictor of the age at diagnosis of LUAD, and rs10057302 was associated with overall survival in LUSC. Furthermore, NSCLC carriers of rs11568821 had a higher risk of death compared to carriers of CC genotype.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Xiangbin Jia, Shujie Zhang, Senwei Tan, Bing Du, Mei He, Haisong Qin, Jia Chen, Xinyu Duan, Jingsi Luo, Fei Chen, Luping Ouyang, Jian Wang, Guodong Chen, Bin Yu, Ge Zhang, Zimin Zhang, Yongqing Lyu, Yi Huang, Jian Jiao, Jin Yun Helen Chen, Kathryn J. Swoboda, Emanuele Agolini, Antonio Novelli, Chiara Leoni, Giuseppe Zampino, Gerarda Cappuccio, Nicola Brunetti-Pierri, Benedicte Gerard, Emmanuelle Ginglinger, Julie Richer, Hugh McMillan, Alexandre White-Brown, Kendra Hoekzema, Raphael A. Bernier, Evangeline C. Kurtz-Nelson, Rachel K. Earl, Claartje Meddens, Marielle Alders, Meredith Fuchs, Roseline Caumes, Perrine Brunelle, Thomas Smol, Ryan Kuehl, Debra-Lynn Day-Salvatore, Kristin G. Monaghan, Michelle M. Morrow, Evan E. Eichler, Zhengmao Hu, Ling Yuan, Jieqiong Tan, Kun Xia, Yiping Shen, Hui Guo
Summary: This study reports a newly identified neurodevelopmental disorder and suggests the importance of stress granules (SGs) in its pathology. By studying mice and analyzing data from a large number of patients, the researchers found that genetic variants in genes related to SGs were associated with the disorder. These findings provide significant insights into the underlying mechanisms of neurodevelopmental disorders.
Article
Biochemical Research Methods
Zahra Rahaie, Hamid R. Rabiee, Hamid Alinejad-Rokny
Summary: This paper introduces DeepGenePrior, a model based on deep neural networks that prioritizes candidate genes in genetic diseases. By analyzing copy number variants from individuals with autism, schizophrenia, and developmental delay, we identified genes that best distinguish cases from controls. Our findings indicate an increase in brain-expressed genes and genes associated with mouse nervous system phenotypes compared to previous studies. DeepGenePrior is publicly available online to address obstacles in existing gene prioritization studies.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lisa Pavinato, Ehsan Nematian-Ardestani, Andrea Zonta, Silvia De Rubeis, Joseph Buxbaum, Cecilia Mancini, Alessandro Bruselles, Marco Tartaglia, Mauro Pessia, Stephen J. Tucker, Maria Cristina D'Adamo, Alfredo Brusco
Summary: In this study, biallelic missense variants in the KCNK18 gene were identified in a family with three siblings affected by mild-to-moderate ID, ASD, and other neurodevelopment-related features. Functional characterization of the variants showed impaired channel activity, particularly with the alteration of the Ser252 site leading to additive downstream effects. These findings expand the clinical variability associated with altered TRESK function and provide further insight into the relationship between altered function of this ion channel and human disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Samuel Valentini, Francesco Gandolfi, Mattia Carolo, Davide Dalfovo, Lara Pozza, Alessandro Romanel
Summary: Many studies have found associations between common genetic variants and complex diseases, but the biological mechanisms explaining these associations are largely unknown. Common variants often have small effect sizes, suggesting that interactions among multiple variants may be a key genetic component of complex diseases. Polympact is a web-based resource that allows exploring functional relations among human common variants, characterizing over 18 million variants and identifying potential interactions.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Neurosciences
Shadi Shiva, Jalal Gharesouran, Hani Sabaie, Mohammad Reza Asadi, Shahram Arsang-Jang, Mohammad Taheri, Maryam Rezazadeh
Summary: Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder with increasing incidence in recent decades. Recent studies have shown abnormal expression of ERMN and LTN1 genes in ASD patients, suggesting their potential roles in the pathogenesis of this disorder.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Sarah Al-Mazidi, Laila Al-Ayadhi, Fatmah Alqahtany, Amani Abualnaja, Abdullah Alzarroug, Turki Alharbi, Karim Farhat, Ahmad AlMnaizel, Afaf El-Ansary
Summary: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social, stereotypical, and repetitive behaviors. This study examined the level of NLF-1 in ASD children and found a significant decrease in plasma levels compared to neurotypical children. NLF-1 was also significantly correlated with the severity of behavioral symptoms, suggesting it may play a role in the excitability of neurons in ASD.
SCIENTIFIC REPORTS
(2023)
Article
Behavioral Sciences
Jordi Pijuan, Juan Dario Ortigoza-Escobar, Juan Ortiz, Adrian Alcala, Maria Jose Calvo, Mariona Cubells, Cristina Hernando-Davalillo, Francesc Palau, Janet Hoenicka
Summary: Genomic analysis and experimental functional studies identified PLXNA2 and LRRC40 as ASD candidate genes in a complex ASD patient, revealing a novel interaction between their proteins in a common neural network. These findings provide new insights for the pathogenesis of ASD and suggest further investigation of these genes in patients with neurodevelopmental disorders, particularly ASD.
Article
Endocrinology & Metabolism
Francesca Marta Elli, Deborah Mattinzoli, Camilla Lucca, Matteo Piu, Maria A. Maffini, Jole Costanza, Laura Fontana, Carlo Santaniello, Concetta Forino, Donatella Milani, Maria Teresa Bonati, Andrea Secco, Roberto Gastaldi, Carlo Alfieri, Piergiorgio Messa, Monica Miozzo, Maura Arosio, Giovanna Mantovani
Summary: Skeletal disorders are caused by genetic defects that affect the pathways involved in skeletogenesis and growth-plate development. A study identified novel genetic variants associated with skeletal malformations similar to Albright's hereditary osteodystrophy and confirmed their pathogenic impact. The study highlights the importance of interdisciplinary collaboration in rare patients.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Cell Biology
Frederic Ebstein, Sebastien Kuery, Victoria Most, Cory Rosenfelt, Marie-Pier Scott-Boyer, Geeske M. van Woerden, Thomas Besrard, Jonas Johannes Papendorf, Maja Studencka-Turski, Tianyun Wang, Tzung-Chien Hsieh, Richard Golnik, Dustin Baldridge, Cara Forster, Charlotte de Konink, Selina M. W. Teurlings, Virginie Vignard, Richard H. van Jaarsveld, Lesley Ades, Benjamin Cogne, Cyril Mignot, Wallid Deb, Marjolijn C. J. Jongmans, F. Sessions Cole, Marie-Jose H. van den Boogaard, Jennifer A. Wambach, Daniel J. Wegner, Sandra Yang, Vickie Hannig, Jennifer Ann Brault, Neda Zadeh, Bruce Bennetts, Boris Keren, Anne-Claire Gelineau, Zoee Powis, Meghan Towne, Kristine Bachman, Andrea Seeley, Anita E. Beck, Jennifer Morrison, Rachel Westman, Kelly Averill, Theresa Brunet, Judith Haasters, Melissa T. Carter, Matthew Osmond, Patricia G. Wheeler, Francesca Forzano, Shehla Mohammed, Yannis Trakadis, Andrea Accogli, Rachel Harrison, Yiran Guo, Hakon Hakonarson, Sophie Rondeau, Genevieve Baujat, Giulia Barcia, Rene Guenther Feichtinger, Johannes Adalbert Mayr, Martin Preisel, Frederic Laumonnier, Tilmann Kallinich, Alexej Knaus, Bertrand Isidor, Peter Krawitz, Uwe Voelker, Elke Hammer, Arnaud Droit, Evan E. Eichler, Ype Elgersma, Peter W. Hildebrand, Francois Bolduc, Elke Krueger, Stephane Bezieau
Summary: PSMC3 variants disrupt proteasome function and cause proteotoxic stress, leading to neurodevelopmental delay and intellectual disability.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Laurel Truscott, Joanna Gell, Vivian Y. Chang, Hane Lee, Samuel P. Strom, Rex Pillai, Anthony Sisk, Julian A. Martinez-Agosto, Martin Anderson, Noah Federman
PEDIATRIC BLOOD & CANCER
(2017)
Article
Genetics & Heredity
Paul C. Marcogliese, Vandana Shashi, Rebecca C. Spillmann, Nicholas Stong, Jill A. Rosenfeld, Mary Kay Koenig, Julian A. Martinez-Agosto, Matthew Herzog, Agnes H. Chen, Patricia I. Dickson, Henry J. Lin, Moin U. Vera, Noriko Salamon, Damara Ortiz, Elena Infante, Wouter Steyaert, Bart Dermaut, Bruce Poppe, Hyung-Lok Chung, Zhongyuan Zuo, Pei-Tseng Lee, Oguz Kanca, Fan Xia, Yaping Yang, Edward C. Smith, Joan Jasien, Sujay Kansagra, Gail Spiridigliozzi, Mays El-Dairi, Robert Lark, Kacie Riley, Dwight D. Koeberl, Katie Golden-Grant, Shinya Yamamoto, Michael F. Wangler, Ghayda Mirzaa, Dimitri Hemelsoet, Brendan Lee, Stanley F. Nelson, David B. Goldstein, Hugo J. Bellen, Loren D. M. Pena
AMERICAN JOURNAL OF HUMAN GENETICS
(2018)
Article
Genetics & Heredity
Sureni V. Mullegama, Steven D. Klein, Rebecca H. Signer, Eric Vilain, Julian A. Martinez-Agosto
MOLECULAR GENETICS & GENOMIC MEDICINE
(2019)
Article
Genetics & Heredity
Brian D. Friend, Kami Wolfe Schneider, Timothy Garrington, Laurel Truscott, Julian A. Martinez-Agosto, Robert S. Venick, Eileen Tsai Chambers, Patricia Weng, Douglas G. Farmer, Vivian Y. Chang, Noah Federman
MOLECULAR GENETICS & GENOMIC MEDICINE
(2019)
Article
Genetics & Heredity
Steven D. Klein, Dzung C. Nguyen, Viraj Bhakta, Derek Wong, Vivian Y. Chang, Tom B. Davidson, Julian A. Martinez-Agosto
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2019)
Article
Behavioral Sciences
Aaron D. Besterman, Joshua Sadik, Michael J. Enenbach, Fabiola Quintero-Rivera, Mark DeAntonio, Julian A. Martinez-Agosto
Article
Genetics & Heredity
Nathan Kopp, Ina Amarillo, Julian Martinez-Agosto, Fabiola Quintero-Rivera
Summary: NLGN4X is an X-linked postsynaptic scaffolding protein associated with neuropsychiatric disorders. A female proband with NLGN4X microdeletion inherited from her father showed ASD, while her father exhibited psychiatric phenotypes. This case provides further evidence that NLGN4X is sensitive to dosage changes in females.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Genetics & Heredity
Emily K. Mis, Annalisa G. Sega, Rebecca H. Signer, Tracy Cartwright, Weizhen Ji, Julian A. Martinez-Agosto, Stanley F. Nelson, Christina G. S. Palmer, Hane Lee, Thomas Mitzelfelt, Monica Konstantino, Lauren Jeffries, Mustafa K. Khokha, Elysa Marco, Martin G. Martin, Saquib A. Lakhani
Summary: A novel de novo heterozygous NEUROD2 missense variant was found in an adolescent with developmental delay but without seizures, displaying minimal protein activity in functional testing. Another rare NEUROD2 variant identified in an adolescent with developmental delay showed normal NEUROD2 activity, suggesting that NEUROD2 variants can lead to developmental delay without early-onset seizures.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Genetics & Heredity
Fabiola Quintero-Rivera, Celeste C. Eno, Christine Sutanto, Kelly L. Jones, Malgorzata J. M. Nowaczyk, Derek Wong, Dawn Earl, Ghayda Mirzaa, Anita Beck, Julian A. Martinez-Agosto
Summary: NSD1 plays a critical role in microduplication 5q35 syndrome, potentially affecting growth and psychiatric phenotypes by altering mTOR pathway signaling. The study also suggests that leucine supplementation may serve as a potential therapeutic approach to ameliorate the symptoms.
Article
Genetics & Heredity
Celeste C. Eno, Jesper Graakjaer, Dea Svaneby, Mathilde Nizon, Jessica Kianmahd, Rebecca Signer, Julian A. Martinez-Agosto, Fabiola Quintero-Rivera
Summary: Three unrelated patients have similar microdeletions of chromosome 14q32.11 with shared phenotypes, including language and developmental delay. Four overlapping genes in the deletion region are expressed in the brain and have haploinsufficiency scores, suggesting a potential influence on the resulting phenotype. This microdeletion may be associated with developmental and language delay based on the lack of normal variation in this region and the patients' similar phenotypes.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Genetics & Heredity
Thomas W. Frazier, Ritika Jaini, Robyn M. Busch, Matthew Wolf, Tammy Sadler, Patricia Klaas, Antonio Y. Hardan, Julian A. Martinez-Agosto, Mustafa Sahin, Charis Eng
Summary: This study investigated differences in PTEN pathway protein levels in PTEN-ASD, PTEN no-ASD, and macro-ASD patients, and the associations between these protein levels and neurobehavioral functions. Results showed decreased levels of PTEN and S6 in PTEN mutation groups, while reductions in MnSOD and increases in P-S6 were observed in ASD groups. The study suggests that molecular measures contribute significantly to predicting neurobehavioral outcomes.
Article
Genetics & Heredity
Mirko Uljarevic, Thomas W. Frazier, Gaelle Rached, Robyn M. Busch, Patricia Klaas, Siddharth Srivastava, Julian A. Martinez-Agosto, Mustafa Sahin, Charis Eng, Antonio Y. Hardan
Summary: This study provides a comprehensive characterization of distinct RRB domains in individuals with PTEN mutations. Significant group differences were found in RMB, IS, and CI scales, with the PTEN-No ASD group showing lower scores compared to PTEN-ASD and Macro-ASD groups. Despite limitations, important assessment and treatment implications were highlighted in this investigation.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Genetics & Heredity
Yue Huang, Katheryn Grand, Virginia Kimonis, Merlin G. Butler, Suparna Jain, Alden Yen-Wen Huang, Julian A. Martinez-Agosto, Stanley F. Nelson, Pedro A. Sanchez-Lara
Summary: The study reports the first case of PWS associated with a de novo mosaic nonsense variant of the SNRPN gene, suggesting that gene sequencing should be considered in patients with clinical suspicion of PWS.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Cell Biology
Jamie Lee, Joshua Zhang, Maeve Flanagan, Julian A. Martinez, Christopher Cunniff, Nicole Kucine, Ake T. Lu, Amin Haghani, Juozas Gordevicius, Steve Horvath, Vivian Y. Chang
Summary: Bloom syndrome (BSyn) is caused by variants in the BLM gene and manifests as poor growth, sun sensitivity, mild immunodeficiency, diabetes, and increased cancer risk, particularly leukemias. Our study reveals accelerated epigenetic aging in BSyn patients compared to carriers, as evidenced by multiple measures in blood lymphocytes. Additionally, homozygous Blm mice exhibit accelerated methylation age in various tissues according to the brain methylation clock. Overall, Bloom syndrome is associated with accelerated epigenetic aging effects in multiple tissues and significant impact on CpG methylation levels.
Article
Genetics & Heredity
Kim M. Keppler-Noreuil, Julian A. Martinez-Agosto, Louanne Hudgins, John C. Carey
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2017)