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}
}
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Molecular genetic study of japanese patients with X-linked alpha-thalassemia/mental retardation syndrome (ATR-X).

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.

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

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

Mutations in the ZNF41 gene are associated with cognitive deficits: identification of a new candidate for X-linked mental retardation.

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

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

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.

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.

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.

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.
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