Mutations in a putative global transcriptional regulator cause X-linked mental retardation with α-thalassemia (ATR-X syndrome)
@article{Gibbons1995MutationsIA, title={Mutations in a putative global transcriptional regulator cause X-linked mental retardation with $\alpha$-thalassemia (ATR-X syndrome)}, author={Richard J. Gibbons and David J. Picketts and Laurent Villard and Douglas R. Higgs}, journal={Cell}, year={1995}, volume={80}, pages={837-845} }
602 Citations
Molecular genetic study of japanese patients with X-linked alpha-thalassemia/mental retardation syndrome (ATR-X).
- Biology, MedicineAmerican journal of medical genetics
- 2000
The putative zinc finger domain and the helicase domains may have similar functional significance for the function of ATRX.
Splicing mutation in the ATR-X gene can lead to a dysmorphic mental retardation phenotype without alpha-thalassemia.
- BiologyAmerican journal of human genetics
- 1996
It is demonstrated that the mode ofaction of the XNP gene product on globin expression is distinct from its mode of action in brain development and facial morphogenesis and suggest that other dysmorphic mental retardation phenotypes, such as Juberg-Marsidi or some sporadic cases of Coffin-Lowry, could be due to mutations in XNP.
A Point Mutation in the XNP Gene, Associated with an ATR-X Phenotype without α-Thalassemia
- BiologyEuropean journal of human genetics : EJHG
- 1996
A mutation in XNP is reported, segregating in a family presenting an ‘ATR-X’ phenotype without α-thalassemia, that causes a proline to serine transition in the helicase II domain.
ATR-X Syndrome Protein Targets Tandem Repeats and Influences Allele-Specific Expression in a Size-Dependent Manner
- BiologyCell
- 2010
Mutations in the ZNF41 gene are associated with cognitive deficits: identification of a new candidate for X-linked mental retardation.
- Biology, MedicineAmerican journal of human genetics
- 2003
The results suggest that ZNF 41 is critical for cognitive development; further studies aim to elucidate the specific mechanisms by which ZNF41 alterations lead to MR.
Role of ATRX Chromatin Remodelling Factor in α‐Thalassaemia X‐Linked Mental Retardation
- Biology, Medicine
- 2016
Though clinical features of ATR-X syndrome show variability, common characteristics include facial dysmorphism, stunted growth, hypotonia, microcephaly, intellectual disability, mild anaemia with detectable haemoglobin H (HbH) and genital abnormalities.
ATR-X mutations cause impaired nuclear location and altered DNA binding properties of the XNP/ATR-X protein
- BiologyJournal of medical genetics
- 2000
In vitro experiments are used to show that the zinc finger domain can mediate double stranded DNA binding and found that the DNA binding capacity of mutant forms in ATR-X patients is severely reduced, providing insights into the understanding of the functional significance of XNP/ATR- Xmutations.
The alpha-thalassemia/mental retardation syndromes.
- Biology, MedicineMedicine
- 1996
Without a feature such as alpha-thalassemia to pinpoint the area of genome or pathways involved it may prove difficult to identify other, similarly affected genes underlying other forms of mental retardation, but as the human genome project and rapid genome analysis evolve this problem should become less of an obstacle.
Evidence for a new X-linked mental retardation gene in Xp21-Xp22: clinical and molecular data in one family.
- Biology, MedicineAmerican journal of medical genetics
- 1999
Three candidate genes in this region were investigated: the cDNA for kinase Rsk-2 involved in Coffin-Lowry syndrome, the brain-specific exon of a transcript in the DMD locus, and exon 18 of the glycerol kinase gene, which is specific to fetal brain transcripts.
ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome.
- Biology, MedicineHuman molecular genetics
- 1996
The full-length cDNA and predicted structure of the ATRX protein is characterised and comparative analysis shows that it is an entirely new member of the SNF2 subgroup of a superfamily of proteins with similar ATPase and helicase domains.
References
SHOWING 1-10 OF 63 REFERENCES
X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysis.
- Medicine, BiologyAmerican journal of human genetics
- 1992
It is shown that intellectually normal female carriers of this syndrome may be identified by the presence of rare cells containing HbH inclusions in their peripheral blood and by an extremely skewed pattern of X inactivation seen in cells from a variety of tissues.
X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: a new kindred with severe genital anomalies and mild hematologic expression.
- Medicine, BiologyAmerican journal of medical genetics
- 1995
More widespread use of brilliant cresyl blue staining for HbH inclusions in individuals with the facial phenotype of ATR-X and/or ambiguous genitalia may lead to the identification of more affected patients and improved understanding of the clinical spectrum of ATr-X.
Cloning and expression of the murine homologue of a putative human X-linked nuclear protein gene closely linked to PGK1 in Xq13.3.
- BiologyHuman molecular genetics
- 1994
The cloning and characterization of the murine homologue of the XNP suggests that this gene might be involved in neuronal differentiation, and among the different morbid phenotypes assigned to the region, X-linked mental retardation would be the best candidate to be associated with this gene.
Clinical and hematologic aspects of the X-linked α-thalassemia/mental retardation syndrome (ATR-X)
- Medicine
- 1995
The consistency of the main characteristics of this syndrome is demonstrated and the developmental changes in phenotype, in particular the coarsening of the facial appearance, are illustrated and the hematologic findings are shown to vary widely.
Clinical features and molecular analysis of the alpha thalassemia/mental retardation syndromes. II. Cases without detectable abnormality of the alpha globin complex.
- Biology, MedicineAmerican journal of human genetics
- 1990
It is speculated that the locus of this underlying mutation is not closely linked to the alpha globin complex and may encode a trans-acting factor involved in the normal regulation ofalpha globin expression.
Hemoglobin H disease and mental retardation: a new syndrome or a remarkable coincidence?
- Medicine, BiologyThe New England journal of medicine
- 1981
Each of three families of northern European origin contains a mentally retarded son with hemoglobin H (Hb H) disease, suggesting that this form of Hb H disease results from the interaction between an inherited defect of alpha-chain production and one member of the pair in chromosome 16 and a new mutation on the other.
Cloning and characterization of a new human Xq13 gene, encoding a putative helicase.
- BiologyHuman molecular genetics
- 1994
Cl cloning and characterization of a new human Xq13 gene (XH2) is described, extending over a 220 kb genomic stretch between MNK and DXS56, which contains a 4 kb open reading frame and encodes a putative NTP-binding nuclear protein homologous to several members of the helicase II superfamily.
Delineation of the dystonia-parkinsonism syndrome locus in Xq13.
- Biology, MedicineProceedings of the National Academy of Sciences of the United States of America
- 1992
Assignment of DYT3 to a region in Xq13, flanked by loci 4548-7 and DXS159, is further supported by highly significant allelic association between DyT3 and a total of four DNTR loci--PY2-31, PY5-10, 45 48-1, and 4548 -7--located in a region defined by PGK1 andDXS56.
Mutations in the xeroderma pigmentosum group D DNA repair/transcription gene in patients with trichothiodystrophy
- Biology, MedicineNature Genetics
- 1994
This work has identified causative mutations in XPD in four TTD patients and suggested relationships between different domains in the gene and its roles in excision repair and transcription.
A deletion of the human beta-globin locus activation region causes a major alteration in chromatin structure and replication across the entire beta-globin locus.
- BiologyGenes & development
- 1990
The results suggest that the LAR is required for both the erythroid-specific chromatin structure and timing of DNA replication over a large physical distance.