ArticleGenetics in medicine : official journal of the American College of Medical Genetics2017
Enrichment of mutations in chromatin regulators in people with Rett syndrome lacking mutations in MECP2.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02738281 (Rett Syndrome, MECP2 Duplication Disorder, and Rett- Related Disorders Natural History Protocol), which is not on this map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Rett Syndrome, MECP2 Duplication Disorder, and Rett- Related Disorders Natural History Protocol
Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies.American journal of human genetics · 2017Pooled it
- Trial
- Rett syndrome: MECP2 biology, multisystem pathophysiology, and the evolving therapeutic landscape.European journal of pediatrics · 2026Review
- Article
- Genomic insights into Rett syndrome-like features in Bangladeshi participants.Genetics in medicine open · 2025Article
- Rett syndrome.Nature reviews. Disease primers · 2024Review
- Rett syndrome: The Natural History Study journey.Annals of the Child Neurology Society · 2024Review
- Preliminary Study on Clinical Characteristics and Pathogenesis ofPharmacogenomics and personalized medicine · 2024Article
- Article
- Article
- Genotype-phenotype correlations of STXBP1 pathogenic variants and the treatment choices for STXBP1-related disorders in China.BMC medical genomics · 2023Article
- Integrative analysis of multi-omics data to detect the underlying molecular mechanisms for obesity in vivo in humans.Human genomics · 2022Article
- Disruption of MeCP2-TCF20 complex underlies distinct neurodevelopmental disorders.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Insights Into the Emerging Role of Baf53b in Autism Spectrum Disorder.Frontiers in molecular neuroscience · 2022Review
- CHD4 variants are associated with childhood idiopathic epilepsy with sinus arrhythmia.CNS neuroscience & therapeutics · 2021Article
- Technological Improvements in the Genetic Diagnosis of Rett Syndrome Spectrum Disorders.International journal of molecular sciences · 2021Review
- The Role of Thyroid Hormone in the Regulation of Cerebellar Development.Endocrinology and metabolism (Seoul, Korea) · 2021Article
- Rett Syndrome Spectrum in Monogenic Developmental-Epileptic Encephalopathies and Epilepsies: A Review.Genes · 2021Review
- TBL1XR1 Ensures Balanced Neural Development Through NCOR Complex-Mediated Regulation of the MAPK Pathway.Frontiers in cell and developmental biology · 2021Article
- Nuclear receptor corepressors in intellectual disability and autism.Molecular psychiatry · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
purposeRett syndrome (RTT) is a neurodevelopmental disorder caused primarily by de novo mutations in MECP2 and sometimes in CDKL5 and FOXG1. However, some RTT patients lack mutations in these genes.
methodsTwenty-two RTT patients without apparent MECP2, CDKL5, and FOXG1 mutations were subjected to both whole-exome sequencing and single-nucleotide polymorphism array-based copy-number variant (CNV) analyses.
resultsThree patients had MECP2 mutations initially missed by clinical testing. Of the remaining 19, 17 (89.5%) had 29 other likely pathogenic intragenic mutations and/or CNVs (10 patients had 2 or more). Interestingly, 13 patients had mutations in a gene/region previously reported in other neurodevelopmental disorders (NDDs), thereby providing a potential diagnostic yield of 68.4%. These mutations were significantly enriched in chromatin regulators (corrected P = 0.0068) and moderately enriched in postsynaptic cell membrane molecules (corrected P = 0.076), implicating glutamate receptor signaling.
conclusionThe genetic etiology of RTT without MECP2, CDKL5, and FOXG1 mutations is heterogeneous, overlaps with other NDDs, and complicated by a high mutation burden. Dysregulation of chromatin structure and abnormal excitatory synaptic signaling may form two common pathological bases of RTT.Genet Med 19 1, 13-19.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.