Mutations in transcriptional regulator ATRX establish the functional significance of a PHD-like domain

Gibbons, Richard J.; Bachoo, Satvinder; Picketts, David J.; Aftimos, Salim; Asenbauer, B; Bergoffen, JoAnn; Berry, Susan A.; Dahl, Niklas; Fryer, Alan; Keppler, Kim; Kurosawa, Kenji; Levin, Michael; Masuno, Mitsuo; Neri, Giovanni; Pierpont, Mary Ella M; Slaney, Sarah F.; Higgs, Douglas R.

doi:10.1038/ng1097-146

Cited by 191 publications

(138 citation statements)

References 16 publications

Supporting

Mentioning

135

Contrasting

Unclassified

Order By: Relevance

“…Direct mutation analysis (Figure 3), however, revealed a weak positive signal for the mother (1-1) although both sisters (2-2, 2-3) were negative for the mutation. Serial dilutions showed that the signal in the mother was 1/64 of that in the proband (2)(3)(4)(5). Repeated analysis with fresh dilutions of the mother's DNA sample gave identical results.…”

Section: Pedigree 19supporting

confidence: 55%

See 1 more Smart Citation

Germline and gonosomal mosaicism in the ATR-X syndrome

Bachoo

Gibbons

1999

Eur J Hum Genet

Self Cite

View full text Add to dashboard Cite

We have identified two females who are mosaic for an ATRX mutation. One case, in whom the mutation was undetectable in peripheral blood and buccal cells, has two affected sons and is therefore presumed to be a germline mosaic. In another case, the ATRX mutation is weakly detectable in the peripheral blood but only one of her three children who share the diseaseassociated haplotype carries the mutation and therefore it is concluded that she is a gonosomal mosaic. These cases provide the first molecular evidence for the occurrence of post-zygotic mutation in X-linked α thalassaemia mental retardation syndrome. The possibility of germline mosaicism must therefore be considered in the genetic counselling of ATR-X families.

show abstract

Section: Pedigree 19supporting

confidence: 55%

“…5 The numbering adopted in this report is based on U75653; the addition of eight bases at the 5' end corrects this to the transcriptional start site. 6 In pedigree 11 the mutation 961G > A destroys a StyI restriction site CCTTGG and creates an MboI restriction site GATC.…”

Section: Mutation Analysismentioning

confidence: 99%

Germline and gonosomal mosaicism in the ATR-X syndrome

Bachoo

Gibbons

1999

Eur J Hum Genet

Self Cite

View full text Add to dashboard Cite

show abstract

“…3). This comprises a PHDlike zinc finger and an additional C 2 C 2 motif just upstream, which is structurally similar to the GATA1 zinc fingers (Gibbons et al 1997;Argentaro et al 2007) and is highly related to the zinc finger domains of DNA methyltransferases (Argentaro et al 2007). The domain mediates binding to the amino-terminal tail of histone H3 trimethylated at lysine 9 (Dhayalan et al 2011;Eustermann et al 2011;Iwase et al 2011).…”

Section: Characterization Of the Atrx Gene And Its Protein Productmentioning

confidence: 99%

-Thalassemia, Mental Retardation, and Myelodysplastic Syndrome

Gibbons

2012

Cold Spring Harbor Perspectives in Medicine

View full text Add to dashboard Cite

“…Based on this result and published data describing an alternative splicing event involving exon 6, we looked for transcripts with different 5 0 -ends of the XNP/ATR-X gene. 9,10 Here, we describe three alternatively spliced transcripts, which are different in the first two exons of the XNP/ATR-X gene and lead to potential proteins differing in their NH 2 -terminal regions. Two transcripts result from the utilization of different splice donor sites within exon 1 and the third consists of an alternative splicing out of the exon 2.…”

Section: Introductionmentioning

confidence: 99%

Mutation in the 5′ alternatively spliced region of the XNP/ATR-X gene causes Chudley–Lowry syndrome

et al. 2004

View full text Add to dashboard Cite

The Chudley-Lowry syndrome (ChLS, MIM 309490) is an X-linked recessive condition characterized by moderate to severe mental retardation, short stature, mild obesity, hypogonadism, and distinctive facial features characterized by depressed nasal bridge, anteverted nares, inverted-V-shaped upper lip, and macrostomia. The original Chudley -Lowry family consists of three affected males in two generations. Linkage analysis had localized the gene to a large interval, Xp21 -Xq26 and an obligate carrier was demonstrated to have highly skewed X inactivation. The combination of the clinical phenotype, consistent with that of the patients with ATR-X syndrome, the skewed X-inactivation pattern in a carrier female, as well as the mapping interval including band Xq13.3, prompted us to consider the XNP/ATR-X gene being involved in this syndrome. Using RT-PCR analysis, we screened the entire XNP/ATR-X gene and found a mutation in exon 2 (c.109C4T) giving rise to a stop codon at position 37 (p.R37X). Western blot and immunocytochemical analyses using a specific monoclonal antibody directed against XNP/ATR-X showed the protein to be present in lymphoblastoid cells from one affected male, despite the premature stop codon. To explain these discordant results, we further analyzed the 5 0 region of the XNP/ATR-X gene and found three alternative transcripts, which differ in the presence or absence of exon 2, and the length of exon 1. Our data suggest that ChLS is allelic to the ATR-X syndrome with its less severe phenotype being due to the presence of some XNP/ATR-X protein.

show abstract

Mutations in transcriptional regulator ATRX establish the functional significance of a PHD-like domain

Cited by 191 publications

References 16 publications

Germline and gonosomal mosaicism in the ATR-X syndrome

Germline and gonosomal mosaicism in the ATR-X syndrome

-Thalassemia, Mental Retardation, and Myelodysplastic Syndrome

Mutation in the 5′ alternatively spliced region of the XNP/ATR-X gene causes Chudley–Lowry syndrome

Contact Info

Product

Resources

About