Review: Child Psychiatry in the Era of Genomics: The Promise of Translational Genetics Research for the Clinic DOI Creative Commons
Sarah E. Fitzpatrick, Irene Antony, Erika L. Nurmi

и другие.

JAACAP Open, Год журнала: 2024, Номер unknown

Опубликована: Авг. 1, 2024

ObjectiveThere has been remarkable progress in recent years understanding the genetic underpinnings of child psychiatric disorders. Concurrently, testing is becoming increasingly available clinic. However, many clinicians report a lack familiarity with genetics and how might inform clinical evaluation. This review aims to introduce cutting-edge research discuss emerging role tests practice.MethodThis highlights major findings presented at Research Institute 69th American Academy Child Adolescent Psychiatry Annual Meeting.ResultsWe provide an overview critical concepts for discussion advances genetics, focusing on autism spectrum disorders, where whole exome sequencing led identification ∼250 high-confidence risk genes. We describe similar approaches gene discovery are beginning shed light architecture early-onset psychosis, Tourette's disorder, obsessive-compulsive other In addition, we practical limitations pharmacogenetic testing, ethical considerations, barriers testing. Finally, illustrate promise advancing our pathophysiology these disorders.ConclusionThis improve clinicians' knowledge evaluation management disorders potential groundbreaking field shape development new treatments.

Язык: Английский

Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy DOI Creative Commons
Hongbin Zhuang, Zhiyuan Liang,

Guanwei Ma

и другие.

MedComm, Год журнала: 2024, Номер 5(3)

Опубликована: Март 1, 2024

Abstract Autism spectrum disorder (ASD) has become a common neurodevelopmental disorder. The heterogeneity of ASD poses great challenges for its research and clinical translation. On the basis reviewing ASD, this review systematically summarized current status progress pathogenesis, diagnostic markers, interventions ASD. We provided an overview molecular mechanisms identified by multi‐omics studies convergent mechanism in different genetic backgrounds. comorbidities, associated with important physiological metabolic abnormalities (i.e., inflammation, immunity, oxidative stress, mitochondrial dysfunction), gut microbial were reviewed. non‐targeted omics targeting markers also Moreover, we methods behavioral educational interventions, intervention related to technological devices, on medical potential drug targets. This highlighted application high‐throughput emphasized importance seeking homogeneity from exploring convergence disease mechanisms, biomarkers, approaches, proposes that taking into account individuality commonality may be key achieve accurate diagnosis treatment

Язык: Английский

Процитировано

16
Autism-Associated Genes and Neighboring lncRNAs Converge on Key Gene Regulatory Networks DOI Creative Commons
Rebecca Andersen, Maya Talukdar, T. Sakamoto

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

The diversity of genes implicated in autism spectrum disorder (ASD) creates challenges for identifying core pathophysiological mechanisms. Aggregation seven different classes genetic variants ASD, a database we call Consensus-ASD , reveals shared features across distinct types ASD variants. Functional interrogation 19 and 9 neighboring long non-coding RNAs (lncRNAs) using CRISPR-Cas13 strikingly revealed differential gene expression profiles that were significantly enriched other genes. Furthermore, construction regulatory network (GRN) enabled the identification central regulators exhibit convergently altered activity upon disruption. Thus, this study how perturbing ASD-associated can lead to shared, broad dysregulation GRNs with critical relevance ASD. This provides crucial framework understanding diverse genes, including lncRNAs, play convergent roles key neurodevelopmental processes ultimately contribute

Язык: Английский

Процитировано

2
Diencephalic and Neuropeptidergic Dysfunction in Zebrafish with Autism Risk Mutations DOI Creative Commons

Mary E.S. Capps,

Anna J. Moyer,

Claire L. Conklin

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 20, 2024

Abstract Hundreds of human mutations are linked to autism and related disorders, yet the functions many these mutated genes during vertebrate neurodevelopment unclear. We generated 27 zebrafish mutants with presumptive protein-truncating or specific missense variants corresponding autism-risk alleles in 17 genes. observed baseline stimulus-driven behavioral changes at larval stages, as well social behavior differences lines tested juveniles. Imaging whole-brain activity revealed a near identical map for unrelated kmt5b hdlbpa , defined by increased mainly diencephalon. Mutating 7 risk resulted substantial brain size differences. Using RNA sequencing, we further molecular drivers phenotypes, identifying targetable disruptions neuropeptide signaling, neuronal maturation, cell proliferation. This multi-modal screen nominated regions, types, pathways that may contribute susceptibility. Teaser Zebrafish uncovers diencephalon, interaction, neuropeptidergic signaling phenotypes ASD mutants.

Язык: Английский

Процитировано

8
Motile cilia modulate neuronal and astroglial activity in the zebrafish larval brain DOI Creative Commons
Percival P. D’Gama, Inyoung Jeong, Andreas Moe Nygård

и другие.

Cell Reports, Год журнала: 2025, Номер 44(1), С. 115195 - 115195

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1
Autism gene variants disrupt enteric neuron migration and cause gastrointestinal dysmotility DOI Creative Commons
Kate E. McCluskey,

Katherine M. Stovell,

Karen Law

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 6, 2025

The co-occurrence of autism and gastrointestinal distress is well-established, yet the molecular underpinnings remain unknown. identification high-confidence, large-effect genes offers opportunity to identify convergent, underlying biology by studying these in context system. Here we show that expression enriched human prenatal gut neurons their migratory progenitors, suggesting development and/or function may be disrupted autism-associated genetic variants, leading dysfunction. document prevalence issues patients with variants sixteen genes, highlighting dysmotility, consistent potential enteric neuron Using Xenopus tropicalis, individually target five (SYNGAP1, CHD8, SCN2A, CHD2, DYRK1A) observe neuronal progenitor migration for each. Further analysis DYRK1A reveals perturbation causes dysmotility vivo, which can ameliorated treatment either two serotonin signaling modulators, identified vivo drug screening. This work suggests atypical contributes commonly seen individuals a productive therapeutic pathway.

Язык: Английский

Процитировано

1
Impairments of cerebellar structure and function in a zebrafish KO of neuropsychiatric risk gene znf536 DOI Creative Commons
T. Kim, Arkaprava Roychaudhury, Hyun-Taek Kim

и другие.

Translational Psychiatry, Год журнала: 2024, Номер 14(1)

Опубликована: Фев. 8, 2024

Abstract Genetic variants in ZNF536 contribute to the risk for neuropsychiatric disorders such as schizophrenia, autism, and others. The role of this putative transcriptional repressor brain development function is, however, largely unknown. We generated znf536 knockout (KO) zebrafish studied their behavior, anatomy, function. Larval KO showed a reduced ability compete food, resulting decreased total body length size. This phenotype can be rescued by segregating homozygous larvae from wild-type heterozygous siblings, enabling studies adult animals. In zebrafish, we observed significant reductions anxiety-like behavior social interaction. These have cerebellar volume, corresponding populations specific neuronal cells, especially valvular cerebelli (Va). Finally, using Tg[mbp:mgfp] line, identified previously undetected myelin structure located bilaterally within Va, which also displayed reduction volume disorganization zebrafish. findings indicate an important implicate cerebellum pathophysiology disorders.

Язык: Английский

Процитировано

5
The dopamine hypothesis of autism spectrum disorder: A comprehensive analysis of the evidence DOI
Denis Pavǎl

International review of neurobiology, Год журнала: 2023, Номер unknown, С. 1 - 42

Опубликована: Янв. 1, 2023

Язык: Английский

Процитировано

11
Delving into the Complexity of Valproate-Induced Autism Spectrum Disorder: The Use of Zebrafish Models DOI Creative Commons

Diletta Camussi,

Valentina Naef, Letizia Brogi

и другие.

Cells, Год журнала: 2024, Номер 13(16), С. 1349 - 1349

Опубликована: Авг. 14, 2024

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental condition with several identified risk factors, both genetic and non-genetic. Among these, prenatal exposure to valproic acid (VPA) has been extensively associated the development of disorder. The zebrafish, cost- time-effective model, useful for studying ASD features. Using validated VPA-induced zebrafish models, we aimed provide new insights into VPA effects during embryonic identify potential biomarkers ASD-like Dose-response analyses were performed in vivo study larval phenotypes mechanisms underlying neuroinflammation, mitochondrial dysfunction, oxidative stress, microglial cell status, motor behaviour. Wild-type transgenic

Язык: Английский

Процитировано

4
Multi-omics analyses of early-onset familial Alzheimer's disease and Sanfilippo syndrome zebrafish models reveal commonalities in disease mechanisms DOI
Karissa Barthelson, Rachael A. Protzman, Marten F. Snel

и другие.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2025, Номер 1871(3), С. 167651 - 167651

Опубликована: Янв. 9, 2025

Язык: Английский

Процитировано

0
m6A‐mRNA Reader YTHDF2 Identified as a Potential Risk Gene in Autism With Disproportionate Megalencephaly DOI Creative Commons
Sierra S. Nishizaki, Nicholas K. Haghani, Gabriana N. La

и другие.

Autism Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Among autistic individuals, a subphenotype of disproportionate megalencephaly (ASD-DM) seen at three years age is associated with co-occurring intellectual disability and poorer prognoses later in life. However, many the genes contributing to ASD-DM have yet be delineated. In this study, we identified additional candidate aim better define genetic etiology autism. We expanded previously studied sample size individuals ten fold by including probands from Autism Phenome Project Simons Simplex Collection, totaling 766 meeting criteria for or macrocephaly revealing 154 harboring de novo protein-impacting variants. Our findings include 14 high confidence autism seven DM. Five impacted been both DM, CHD8 PTEN. By performing functional network analysis, genes, one implicated (PIK3CA) as well 184 connected ASD DM alone. Using zebrafish, modeled tandem duplication impacting YTHDF2, encoding an N6-methyladenosine (m6A)-mRNA reader, proband. Testing zebrafish CRISPR knockdown led reduced head/brain size, while overexpressing YTHDF2 resulted increased matching that Single-cell transcriptomes gain-of-function larvae point expression Fragile-X-syndrome-associated FMRP-target globally developing brain, providing insight into mechanism underlying phenotypes. additionally discovered variant different gene m6A YTHDC1, our cohort. Though highlight only two cases date, study provides support m6A-RNA modification pathway potentially severe form

Язык: Английский

Процитировано

0