Sex-specific DNA methylation signatures of autism spectrum disorder from whole genome bisulfite sequencing of newborn blood DOI Creative Commons
Julia S. Mouat, Nickilou Y. Krigbaum, Sophia Hakam

et al.

Biology of Sex Differences, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 30, 2025

Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions currently diagnosed through behavioral assessments in childhood, though neuropathological changes begin utero. ASD more commonly males, disparity attributed to both biological sex differences and diagnostic biases. Identifying molecular biomarkers, such as DNA methylation signatures, could provide objective screening for ASD-risk newborns, allowing early intervention. Epigenetic dysregulation has been reported multiple tissues from newborns who are later with ASD, but this the first study investigate sex-specific signatures newborn blood, an accessible widely banked tissue. We assayed blood typically developing (TD) individuals (discovery set n = 196, replication 90) using whole genome bisulfite sequencing (WGBS). Sex-stratified differentially methylated regions (DMRs) were assessed replication, comparisons by sex, overlaps DMRs other tissues, enrichment processes SFARI genes. found that sexes significantly replicated independent cohort enriched hypomethylation compared TD samples, well location promoters, CpG islands, island shores. By comparing female male we most sex-associated also individuals, alongside additional ASD-specific differences. Female-specific X chromosomal location. Across sexes, overlapped umbilical cord placenta not post-mortem cerebral cortex. all (females) known genes (both sexes). Overall, identified signature supported protective effect highlighted convergence epigenetic genetic newborns. Despite study's limitations, particularly sample sizes, our results demonstrate potential emphasize importance sex-stratification future studies.

Language: Английский

The long way to diagnosis: Attention Disorder, Alcohol Addiction or Congenital Disorder of Glycosylation?-A case report DOI
Timo Jendrik Faustmann, Lukas Hensel,

Armin Bahic

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Abstract Attention deficit hyperactivity disorder (ADHD) is a relatively common in clinical psychiatry. Patients often suffer from symptoms long before the diagnosis due to an overlap with other psychiatric differential diagnosis. Importantly, alcohol addiction and illicit drug dependence withdrawal mimicking ADHD should be ruled out. Here we present rare case of young female patient extremely high carbohydrate-deficient transferrin (CDT) 19,6% (< 1,3%) indicating presence congenital glycosylation (CDG). A thorough diagnostic workup excluded as cause constantly CDT levels. The test was positive mutation affecting site. Nevertheless, can metabolic disorders which considered. Further, substance-use (SUD) are critical potentially complicated concerning procedures treatment ADHD.

Language: Английский

Citations

0
Exploring potential key genes and disease mechanisms in Εarly-onset genetic epilepsy via integrated bioinformatics analysis DOI Creative Commons

Vasiliki Boulaki,

Spiros Efthimiopoulos, Nicholas Κ. Moschonas

et al.

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106888 - 106888

Published: April 1, 2025

Epilepsy is a severe common neurological disease affecting all ages. with onset before the age of 5 years, designated early-onset epilepsy (EOE), special importance. According to previous studies, genetic factors contribute significantly pathogenesis EOE that remains unclear and must be explored. So, list 229 well-selected EOE-associated genes expressed in brain was created for investigation molecular mechanisms involved its pathogenesis. Enrichment analysis showed among significant pathways were nicotine addiction, GABAergic synapse, synaptic vesicle cycle, regulation membrane potential, cholinergic dopaminergic morphine addiction. Performing an integrated as well protein-protein interaction network-based approaches use GO, KEGG, ClueGO, cytoHubba 3 network metrics, 12 hub identified, seven which, CDKL5, GABRA1, KCNQ2, KCNQ3, SCN1A, SCN8A STXBP1, identified key (via Venn diagram analysis). These are mostly enriched SNARE interactions vesicular transport, potential exocytosis. Clustering PPI via MCODE functional modules, indicating also other such N-Glycan biosynthesis protein N-linked glycosylation, retrograde endocannabinoid signaling, mTOR signaling aminoacyl-tRNA biosynthesis. Drug-gene number drugs medications EOE, which non-FDA approved azetukalner (under clinical development), indiplon ICA-105665 FDA retigabine, ganaxolone methohexital.

Language: Английский

Citations

0
Neuronal CDK5RAP3 deficiency leads to encephalo-dysplasia via upregulation of N-glycosylases and glycogen deposition DOI Creative Commons
Fanghui Chen,

Minghui Xiang,

Zhipeng Wang

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 6, 2025

Abstract CDK5RAP3 is a binding protein of CDK5 activating proteins and also one the key co-factors E3 enzyme in UFMylation system. Several reports have implicated involvement other components system neuronal development multiple psychiatric disorders. However, precise role neurons remains elusive. In this study, we generated neuron-specific knockout mice (CDK5RAP F/F : Nestin-Cre). conditional (CDK5RAP3 CKO) exhibited severe encephalo-dysplasia slower developmental trajectory compared to wild-type (WT) succumbed postnatal demise by day 14. Transcriptome sequencing unveiled that deficiency affects synapse formation, transmembrane trafficking physiological programs brain. Morphological analysis demonstrated leads increased SLC17A6 N-glycosylase (RPN1 ALG2) expression, while causing endoplasmic reticulum (ER) stress. vitro experiments utilizing ROSA26-ERT2Cre MEFs were conducted elucidate similar mechanism following deletion. Both vivo vitro, significantly expression N-glycosylases ALG2), as well total amount glycoproteins. may potentially maintain balance enhancing degradation RPN1 ALG2 through proteolytic pathways autophagy. This study underscores indispensable sheds new light on drug discovery endeavors targeting early brain abnormalities.

Language: Английский

Citations

0
The long way to diagnosis: attention disorder, alcohol addiction or congenital disorder of glycosylation? A case report DOI Creative Commons
Timo Jendrik Faustmann, Lukas Hensel,

Armin Bahic

et al.

BMC Psychiatry, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 29, 2025

Language: Английский

Citations

0
Sex-specific DNA methylation signatures of autism spectrum disorder from whole genome bisulfite sequencing of newborn blood DOI Creative Commons
Julia S. Mouat, Nickilou Y. Krigbaum, Sophia Hakam

et al.

Biology of Sex Differences, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 30, 2025

Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions currently diagnosed through behavioral assessments in childhood, though neuropathological changes begin utero. ASD more commonly males, disparity attributed to both biological sex differences and diagnostic biases. Identifying molecular biomarkers, such as DNA methylation signatures, could provide objective screening for ASD-risk newborns, allowing early intervention. Epigenetic dysregulation has been reported multiple tissues from newborns who are later with ASD, but this the first study investigate sex-specific signatures newborn blood, an accessible widely banked tissue. We assayed blood typically developing (TD) individuals (discovery set n = 196, replication 90) using whole genome bisulfite sequencing (WGBS). Sex-stratified differentially methylated regions (DMRs) were assessed replication, comparisons by sex, overlaps DMRs other tissues, enrichment processes SFARI genes. found that sexes significantly replicated independent cohort enriched hypomethylation compared TD samples, well location promoters, CpG islands, island shores. By comparing female male we most sex-associated also individuals, alongside additional ASD-specific differences. Female-specific X chromosomal location. Across sexes, overlapped umbilical cord placenta not post-mortem cerebral cortex. all (females) known genes (both sexes). Overall, identified signature supported protective effect highlighted convergence epigenetic genetic newborns. Despite study's limitations, particularly sample sizes, our results demonstrate potential emphasize importance sex-stratification future studies.

Language: Английский

Citations

0