ATR-X syndrome

A hereditary X-linked syndrome that occurs almost exclusively in males and affects multiple organ systems. In addition to intellectual disability and mild alpha-thalassemia, affected individuals may have distinct FACIES, ear, nose, and mouth abnormalities, MICROCEPHALY; ANEMIA; GASTROESOPHAGEAL REFLUX; CONSTIPATION and UROGENITAL ABNORMALITIES. Mutations and duplications in the ATRX gene have been identified. OMIM: 301040

Also Known As:

ATR non deletion type; ATR, Nondeletion Type; ATRX Syndrome; Alpha Thalassemia X-Linked Intellectual Disability Syndrome; Alpha Thalassemia X-Linked Mental Retardation Syndrome; Alpha Thalassemia-Mental Retardation, X-Linked; Alpha thalassemia mental retardation syndrome, non deletion type, X-linked; Alpha-Thalassemia-Mental Retardation Syndrome, Nondeletion Type; Alpha-Thalassemia-Mental Retardation Syndrome, Nondeletion Type, X-Linked; Alpha-thalassemia X-linked mental retardation syndrome; X-Linked Alpha-Thalassemia Mental Retardation Syndrome; X-linked alpha thalassemia mental retardation syndrome; XLMR-Hypotonic Face Syndrome

Networked: 76 relevant articles (2 outcomes, 9 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Cognitive Dysfunction
2.	Disease Progression
3.	Neoplasms (Cancer)
4.	ATR-X syndrome
5.	X-Linked Mental Retardation (Mental Retardation, X Linked)

Experts

1.	Gibbons, Richard J: 9 articles (01/2022 - 02/2004)
2.	Higgs, Douglas R: 7 articles (01/2022 - 02/2004)
3.	Bérubé, Nathalie G: 7 articles (01/2020 - 01/2008)
4.	Shioda, Norifumi: 5 articles (10/2020 - 06/2011)
5.	Wada, Takahito: 4 articles (10/2020 - 04/2009)
6.	Picketts, David J: 4 articles (11/2016 - 05/2004)
7.	Heaphy, Christopher M: 3 articles (01/2022 - 07/2012)
8.	Singhi, Aatur D: 3 articles (01/2022 - 01/2018)
9.	Yabuki, Yasushi: 3 articles (10/2020 - 01/2018)
10.	Fukunaga, Kohji: 3 articles (09/2018 - 06/2011)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to ATR-X syndrome:

1.	LigandsIBA 09/18/2018 - "SA4503, A Potent Sigma-1 Receptor Ligand, Ameliorates Synaptic Abnormalities and Cognitive Dysfunction in a Mouse Model of ATR-X Syndrome."
2.	Sigma-1 ReceptorIBA 09/18/2018 - "SA4503, A Potent Sigma-1 Receptor Ligand, Ameliorates Synaptic Abnormalities and Cognitive Dysfunction in a Mouse Model of ATR-X Syndrome."
3.	SA 4503IBA 09/18/2018 - "SA4503, A Potent Sigma-1 Receptor Ligand, Ameliorates Synaptic Abnormalities and Cognitive Dysfunction in a Mouse Model of ATR-X Syndrome."
4.	Proteins (Proteins, Gene)FDA Link 11/01/2023 - "Indeed, numerous helicases such as senataxin (SETX), Aquarius (AQR), WRN, BLM, RTEL1, PIF1, FANCM, ATRX (alpha-thalassemia/mental retardation, X-linked), CasDinG, and several DEAD/H-box proteins are reported to resolve R-loops; while other helicases, such as Cas3 and UPF1, are reported to stimulate R-loop formation. " 01/01/2023 - "Assessment of death domain-associated protein 6/alpha-thalassemia/mental retardation X-linked and alternative lengthening of telomeres are promising novel prognostic markers. " 01/01/2023 - "ALT is genetically associated with somatic alterations in alpha-thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) genes. " 01/01/2021 - "Whole-exome sequencing recently has shown very frequent somatic mutations in the alpha-thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) genes in PanNETs. " 06/01/2013 - "Relating the cause of ATR-X syndrome to the function of the protein ATRX is a case in point. "
5.	Biomarkers (Surrogate Marker)IBA 01/01/2023 - "Recent studies have identified alterations in death domain-associated protein 6 (DAXX) and alpha-thalassemia/mental retardation X-linked (ATRX), as well as alternative lengthening of telomeres (ALT), as promising prognostic biomarkers. " 11/01/2022 - "Recent studies have identified alterations in death domain-associated protein 6 (DAXX) and alpha-thalassemia/mental retardation X-linked (ATRX), as well as alternative lengthening of telomeres (ALT), as promising prognostic biomarkers. " 01/01/2022 - "Recent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). " 09/01/2022 - "Several putative prognostic and/or predictive biomarkers (eg, alternative lengthening of telomeres, alpha-thalassemia/mental retardation, X-linked (ATRX)/Death Domain Associated Protein (DAXX) loss) have been independently validated. " 01/01/2022 - "These studies have highlighted that sporadic NF-PanNETs displaying biomarkers associated with disease progression and poor prognosis, such as alternative lengthening of telomeres, inactivating alpha thalassemia/mental retardation X-linked (ATRX) or death domain-associated protein (DAXX) gene mutations, or copy number variations, more often display alpha cell characteristics. "
6.	Histones (Histone)IBA 07/01/2017 - "In this study, we characterize the Arabidopsis thaliana Alpha Thalassemia-mental Retardation X-linked (ATRX) ortholog and show that ATRX is involved in histone H3 deposition. " 01/01/2022 - "Our results indicate that the histone binding and chromatin remodeling functions of ATRX play non-redundant roles in neurodevelopment, and when mutated lead to ATRX syndrome through separate regulatory pathways." 01/01/2018 - "We highlight findings from our recent study showing that the deposition of the histone variant H3.3 by the alpha-thalassemia mental retardation X-linked protein (ATRX) and the death domain associated protein (DAXX) chromatin remodeling complex regulates DNA repair synthesis during homologous recombination." 01/01/2018 - "ATRX (alpha thalassemia/mental retardation X-linked) complexes with DAXX to deposit histone variant H3.3 into repetitive heterochromatin. " 06/12/2011 - "Notably, H3K9me3-pocket mutants and ATR-X syndrome mutants are defective in both H3K9me3 binding and localization at pericentromeric heterochromatin; thus, we have discovered a unique histone-recognition mechanism underlying the ATR-X etiology."
7.	Isocitrate Dehydrogenase (Isocitrate Dehydrogenase (NAD+))IBA 03/29/2016 - "IDH mutation (isocitrate dehydrogenase) and ATRX (alpha-thalassemia/mental retardation, X-linked) loss/mutation occur in association and may represent early genetic alterations in the development of gliomas. " 02/01/2021 - "Immunohistochemistry analyses for isocitrate dehydrogenase gene 1 (IDH1), alpha thalassemia mental retardation X-linked gene (ATRX), Ki-67, and p53 protein expression were performed. " 04/01/2019 - "Immunohistochemistry (IHC) was performed on the tumors using antibodies directed against the gene products of R132H mutant isocitrate dehydrogenase 1 (IDH1), alpha-thalassemia/mental retardation X-linked (ATRX), p53, H3K27M, H3K27me3, and V600E mutant BRAF. " 11/15/2023 - "This study aimed to determine the presence of significant and nonsense mutations in telomerase reverse transcriptase (TERT), alpha-thalassemia/mental retardation, X-linked (ATRX), O-6-methylguanine-DNA methyltransferase (MGMT), and isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) genes using the Next-Generation Sequencing (NGS) method. " 07/01/2022 - "The aim of our study was to evaluate isocitrate dehydrogenase 1 and 2 (IDH1, IDH2), telomerase reverse transcriptase (TERT), O-6- methylguanine-DNA methyltransferase (MGMT) and alpha-thalassemia/mental retardation, X-linked (ATRX) genes with next-generation sequencing (NGS) to find potential pathological mutations and their effect on survival. "
8.	MethyltransferasesIBA 10/12/2017 - "We also evaluated the protein loss of O-6-methylguanine-DNA methyltransferase (MGMT) and alpha-thalassemia/mental retardation, X-linked (ATRX) during disease recurrence. " 11/15/2023 - "This study aimed to determine the presence of significant and nonsense mutations in telomerase reverse transcriptase (TERT), alpha-thalassemia/mental retardation, X-linked (ATRX), O-6-methylguanine-DNA methyltransferase (MGMT), and isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) genes using the Next-Generation Sequencing (NGS) method. " 07/01/2022 - "The aim of our study was to evaluate isocitrate dehydrogenase 1 and 2 (IDH1, IDH2), telomerase reverse transcriptase (TERT), O-6- methylguanine-DNA methyltransferase (MGMT) and alpha-thalassemia/mental retardation, X-linked (ATRX) genes with next-generation sequencing (NGS) to find potential pathological mutations and their effect on survival. " 04/01/2013 - "Over the last decade it has become increasingly clear that mutations of genes involved in epigenetic mechanism, such as DNA methyltransferases, methyl-binding domain proteins, histone deacetylases, histone methylases and members of the SWI/SNF family of chromatin remodelers are linked to human disorders, including Immunodeficiency Centromeric instability Facial syndrome 1, Rett syndrome, Rubinstein-Taybi syndrome, Sotos syndrome or alpha-thalassemia/mental retardation X-linked syndrome, among others. "
9.	Telomerase (Telomerase Reverse Transcriptase)IBA 11/15/2023 - "This study aimed to determine the presence of significant and nonsense mutations in telomerase reverse transcriptase (TERT), alpha-thalassemia/mental retardation, X-linked (ATRX), O-6-methylguanine-DNA methyltransferase (MGMT), and isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) genes using the Next-Generation Sequencing (NGS) method. " 07/01/2022 - "The aim of our study was to evaluate isocitrate dehydrogenase 1 and 2 (IDH1, IDH2), telomerase reverse transcriptase (TERT), O-6- methylguanine-DNA methyltransferase (MGMT) and alpha-thalassemia/mental retardation, X-linked (ATRX) genes with next-generation sequencing (NGS) to find potential pathological mutations and their effect on survival. "
10.	ChromatinIBA 01/01/2017 - "Alpha thalassemia/mental retardation X-linked syndrome (ATR-X) is caused by a mutation at the chromatin regulator gene ATRX. " 01/01/2022 - "ATRX is a chromatin remodeler, which is mutated in ATRX syndrome, a neurodevelopmental disorder. " 01/01/2020 - "Alpha-thalassemia/mental retardation, X-linked, or ATRX, is an autism susceptibility gene that encodes a chromatin remodeler. " 01/01/2023 - "ATRX (alpha-thalassemia mental retardation X-linked) is one of the most frequently mutated tumor suppressor genes in human cancers, especially in glioma, and recent findings indicate roles for ATRX in key molecular pathways, such as the regulation of chromatin state, gene expression, and DNA damage repair, placing ATRX as a central player in the maintenance of genome stability and function. " 01/01/2018 - "Sequencing studies of PanNETs have identified alterations in death domain-associated protein (DAXX) and alpha-thalassemia/mental retardation X-linked chromatin remodeler (ATRX). "

Therapies and Procedures

1.	Oral Administration 10/08/2020 - "Oral administration of 5-ALA improved cognitive dysfunction in an ATR-X syndrome model mouse, and language ability in an ATR-X syndrome patient. "
2.	Therapeutics 09/18/2018 - "These results indicate that the rescue of dendritic spine abnormalities through the activation of Sig-1R has a potential for post-diagnostic therapy in ATR-X syndrome." 01/01/2018 - "Targeting G-quadruplex DNA as cognitive function therapy for ATR-X syndrome."