De novo mutations of the gene encoding the histone acetyltransferase KAT6B cause Genitopatellar syndrome
Publication year
2012Source
American Journal of Human Genetics, 90, 2, (2012), pp. 290-294ISSN
Publication type
Article / Letter to editor

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Organization
Human Genetics
Urology
Journal title
American Journal of Human Genetics
Volume
vol. 90
Issue
iss. 2
Page start
p. 290
Page end
p. 294
Subject
IGMD 3: Genomic disorders and inherited multi-system disorders; IGMD 9: Renal disorder; NCMLS 6: Genetics and epigenetic pathways of disease IGMD 3: Genomic disorders and inherited multi-system disorders; ONCOL 3: Translational researchAbstract
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.
This item appears in the following Collection(s)
- Academic publications [188575]
- Faculty of Medical Sciences [74223]
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