Research Themes in KAT6A Syndrome: A Scoping Review DOI Creative Commons
Tanya Tripathi, Miya St John, Jordan Wright

и другие.

DNA, Год журнала: 2025, Номер 5(2), С. 21 - 21

Опубликована: Апрель 27, 2025

Pathogenic variants in the KAT6A gene cause syndrome, a neurodevelopmental disorder characterised by intellectual disability (ID), developmental delay, speech and language challenges, feeding difficulties, skeletal abnormalities. This scoping review synthesises current knowledge on identifies key research themes, supports mission of advocacy groups like KAT6 Foundation. A systematic search five databases (Ovid MEDLINE, Ovid EMBASE, PubMed, Web Science, Scopus) was conducted from 1990 to 2024, including peer-reviewed articles, preprints, conference abstracts published 2022 onward. Of 771 citations retrieved, 111 full-text articles were reviewed, with 62 meeting inclusion criteria. Data synthesised into six themes: (1) genotype phenotype map, revealing broad phenotypic spectrum common features ID, absent speech, craniofacial dysmorphism, as well rare such severe aplastic anaemia pancraniosynostosis; (2) profile, detailing communication deficits, sleep disturbances, impaired adaptive functioning; (3) epigenetic roles KAT6A, highlighting its critical function histone acetylation, chromatin remodelling, regulation; (4) molecular biomarkers, identifying distinct DNA methylation episignatures dysregulated cellular pathways; (5) drug discovery, preliminary studies suggesting that pantothenate L-carnitine may mitigate mitochondrial dysfunction acetylation while RSPO2 overexpression reverses cognitive impairment animal models; (6) overlap Rett syndrome KAT6B-related disorders. underscores complexity variability need for multidisciplinary approaches improving diagnosis, management, development therapies. Future should focus longitudinal studies, underrepresented phenotypes, biomarker identification, robust therapeutic trials enhance outcomes affected individuals their families.

Язык: Английский

Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application DOI Creative Commons
Yang Chen, Rui Liang, Yong Li

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Дек. 4, 2024

Abstract The dynamic regulation of chromatin accessibility is one the prominent characteristics eukaryotic genome. inaccessible regions are mainly located in heterochromatin, which multilevel compressed and access restricted. remaining accessible loci generally euchromatin, have less nucleosome occupancy higher regulatory activity. opening most important prerequisite for DNA transcription, replication, damage repair, regulated by genetic, epigenetic, environmental, other factors, playing a vital role multiple biological progresses. Currently, based on susceptibility difference occupied or free to enzymatic cleavage, solubility, methylation, transposition, there many methods detect both bulk single-cell level. Through combining with high-throughput sequencing, genome-wide landscape tissues cells types also been constructed. feature distinct different states. Research network crucial uncovering secret various processes. In this review, we comprehensively introduced major functions mechanisms variation physiological pathological processes, meanwhile, targeted therapies dynamics summarized.

Язык: Английский

Процитировано

4
Epigene functional diversity: isoform usage, disordered domain content, and variable binding partners DOI Creative Commons
Leroy Bondhus, Aileen A. Nava,

Isabelle S. Liu

и другие.

Epigenetics & Chromatin, Год журнала: 2025, Номер 18(1)

Опубликована: Фев. 1, 2025

Epigenes are defined as proteins that perform post-translational modification of histones or DNA, reading modifications, form complexes with epigenetic factors changing the general structure chromatin. This specialized group is responsible for controlling organization genomic DNA in a cell-type specific fashion, normal development spatial and temporal fashion. Moreover, mutations epigenes have been implicated causal germline pediatric disorders driver cancer. Despite their importance to human disease, date, there has not systematic analysis sources functional diversity at large. Epigenes' unique functions require assembly pools within nucleus suggest amino acid composition would enriched features enable efficient chromatin transcription, splicing, modifications. In this study, we assess stemming from gene structure, isoforms, protein domains, multiprotein complex formation drive established epigenes. We found structural variable roles depending on cellular environmental context. First, significantly larger more exons compared non-epigenes which contributes increased isoform diversity. Second participate multimeric than non-epigenes. Thirdly, given proposed membraneless organelles, show substantially intrinsically disordered regions (IDRs). Additionally, assessed specificity expression profiles showed ubiquitously expressed consistent enrichment syndromes intellectual disability, multiorgan dysfunction, developmental delay. Finally, L1000 dataset, identify drugs can potentially be used modulate these genes. Here significant differences usage, domain content, binding partners between using various genomics datasets Ensembl, ENCODE, GTEx, HPO, LINCS L1000, BrainSpan. Our results contribute new knowledge growing field focused developing targeted therapies diseases caused by epigene mutations, such chromatinopathies cancers.

Язык: Английский

Процитировано

0
Comprehensive review and outline of genotypes and phenotypes of Arboleda-Tham syndrome spectrum: insights from novel variants DOI
Sahar Bayat, Milad Gholami, Hamidreza Khodadadi

и другие.

Molecular Biology Reports, Год журнала: 2025, Номер 52(1)

Опубликована: Фев. 18, 2025

Язык: Английский

Процитировано

0
Research Themes in KAT6A Syndrome: A Scoping Review DOI Creative Commons
Tanya Tripathi, Miya St John, Jordan Wright

и другие.

DNA, Год журнала: 2025, Номер 5(2), С. 21 - 21

Опубликована: Апрель 27, 2025

Pathogenic variants in the KAT6A gene cause syndrome, a neurodevelopmental disorder characterised by intellectual disability (ID), developmental delay, speech and language challenges, feeding difficulties, skeletal abnormalities. This scoping review synthesises current knowledge on identifies key research themes, supports mission of advocacy groups like KAT6 Foundation. A systematic search five databases (Ovid MEDLINE, Ovid EMBASE, PubMed, Web Science, Scopus) was conducted from 1990 to 2024, including peer-reviewed articles, preprints, conference abstracts published 2022 onward. Of 771 citations retrieved, 111 full-text articles were reviewed, with 62 meeting inclusion criteria. Data synthesised into six themes: (1) genotype phenotype map, revealing broad phenotypic spectrum common features ID, absent speech, craniofacial dysmorphism, as well rare such severe aplastic anaemia pancraniosynostosis; (2) profile, detailing communication deficits, sleep disturbances, impaired adaptive functioning; (3) epigenetic roles KAT6A, highlighting its critical function histone acetylation, chromatin remodelling, regulation; (4) molecular biomarkers, identifying distinct DNA methylation episignatures dysregulated cellular pathways; (5) drug discovery, preliminary studies suggesting that pantothenate L-carnitine may mitigate mitochondrial dysfunction acetylation while RSPO2 overexpression reverses cognitive impairment animal models; (6) overlap Rett syndrome KAT6B-related disorders. underscores complexity variability need for multidisciplinary approaches improving diagnosis, management, development therapies. Future should focus longitudinal studies, underrepresented phenotypes, biomarker identification, robust therapeutic trials enhance outcomes affected individuals their families.

Язык: Английский

Процитировано

0