Journal
AMERICAN JOURNAL OF HUMAN GENETICS
Volume 90, Issue 2, Pages 290-294Publisher
CELL PRESS
DOI: 10.1016/j.ajhg.2011.11.024
Keywords
-
Categories
Funding
- Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre
- King's College London and King's College Hospital NHS Foundation Trust
- Netherlands Organisation for Health Research and Development (ZonMW) [916.86.016]
- National Institute for Health Research [NF-SI-0507-10379] Funding Source: researchfish
Ask authors/readers for more resources
Genitopatellar syndrome (GPS) is a rare disorder in which patellar aplasia or hypoplasia is associated with external genital anomalies and severe intellectual disability. Using an exome-sequencing approach, we identified de novo mutations of KAT6B in five individuals with GPS; a single nonsense variant and three frameshift indels, including a 4 bp deletion observed in two cases. All identified mutations are located within the terminal exon of the gene and are predicted to generate a truncated protein product lacking evolutionarily conserved domains. KAT6B encodes a member of the MYST family of histone acetyltranferases. We demonstrate a reduced level of both histone H3 and H4 acetylation in patient-derived cells suggesting that dysregulation of histone acetylation is a direct functional consequence of GPS alleles. These findings define the genetic basis of GPS and illustrate the complex role of the regulation of histone acetylation during development.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available