TY - JOUR
T1 - De novo mutations of the gene encoding the histone acetyltransferase KAT6B cause genitopatellar syndrome
AU - Simpson, Michael A.
AU - Deshpande, Charu
AU - Dafou, Dimitra
AU - Vissers, Lisenka E.L.M.
AU - Woollard, Wesley J.
AU - Holder, Susan E.
AU - Gillessen-Kaesbach, Gabriele
AU - Derks, Ronny
AU - White, Susan M.
AU - Cohen-Snuijf, Ruthy
AU - Kant, Sarina G.
AU - Hoefsloot, Lies H.
AU - Reardon, Willie
AU - Brunner, Han G.
AU - Bongers, Ernie M.H.F.
AU - Trembath, Richard C.
PY - 2012/2/10
Y1 - 2012/2/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84857044289&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2011.11.024
DO - 10.1016/j.ajhg.2011.11.024
M3 - Journal articles
C2 - 22265017
AN - SCOPUS:84857044289
SN - 0002-9297
VL - 90
SP - 290
EP - 294
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 2
ER -