The defining DNA methylation signature of Floating-Harbor Syndrome

@article{Hood2016TheDD,
  title={The defining DNA methylation signature of Floating-Harbor Syndrome},
  author={Rebecca L. Hood and Laila Cigana Schenkel and Sarah M. Nikkel and Peter J. Ainsworth and Guillaume Par{\'e} and Kym M. Boycott and Dennis E. Bulman and Bekim Sadikovic},
  journal={Scientific Reports},
  year={2016},
  volume={6}
}
Floating-Harbor syndrome (FHS) is an autosomal dominant genetic condition characterized by short stature, delayed osseous maturation, expressive language impairment, and unique facial dysmorphology. We previously identified mutations in the chromatin remodeling protein SRCAP (SNF2-related CBP Activator Protein) as the cause of FHS. SRCAP has multiple roles in chromatin and transcriptional regulation; however, specific epigenetic consequences of SRCAP mutations remain to be described. Using high… 

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References

SHOWING 1-10 OF 35 REFERENCES

Identification of a methylation profile for DNMT1-associated autosomal dominant cerebellar ataxia, deafness, and narcolepsy

This report identifies robust changes in the DNA methylation patterns in ADCA-DN patients, which is an important step towards elucidating disease pathogenesis.

Multilocus loss of DNA methylation in individuals with mutations in the histone H3 Lysine 4 Demethylase KDM5C

Genetic alterations in patient samples carrying a mutation in a gene involved in the regulation of histone modifications are identified, for the first time, and support the concept that DNA methylation and H3 lysine 4 methylation are functionally interdependent.

Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease.

There is a direct link between loss of acetyl transferase activity and RSTS, which indicates that the disorder is caused by aberrant chromatin regulation and the search for mutations to the EP300 gene was extended and showed that mutations in EP300 also cause this disorder.

The phenotype of Floating–Harbor syndrome in 10 patients

Clinical findings in 10 typically affected individuals ranging in age from 7 to 34 years and a mother and daughter who display some features of FHS are reported and microarray analysis in eight of the patients provided no evidence that FHS is caused by a large‐scale copy‐number genomic change.

Mutations in the JARID1C gene, which is involved in transcriptional regulation and chromatin remodeling, cause X-linked mental retardation.

The results suggest that JARID1C mutations are a relatively common cause of XLMR and that this gene might play an important role in human brain function.

Mutations in ATRX, encoding a SWI/SNF-like protein, cause diverse changes in the pattern of DNA methylation

A goal of molecular genetics is to understand the relationship between basic nuclear processes, epigenetic changes and the numerous proteins that orchestrate these effects. One such protein, ATRX,

Lsh, a member of the SNF2 family, is required for genome-wide methylation.

It is reported here, however, that Lsh(-/-) mice show substantial loss of methylation throughout the genome, which suggests that global genomic methylation is not absolutely required for normal embryogenesis.