Mutations in KAT6B, encoding a histone acetyltransferase, cause Genitopatellar syndrome.

TitleMutations in KAT6B, encoding a histone acetyltransferase, cause Genitopatellar syndrome.
Publication TypeJournal Article
Year of Publication2012
AuthorsCampeau, PM, Kim, JC, Lu, JT, Schwartzentruber, JA, Abdul-Rahman, OA, Schlaubitz, S, Murdock, DM, Jiang, M-M, Lammer, EJ, Enns, GM, Rhead, WJ, Rowland, J, Robertson, SP, Cormier-Daire, V, Bainbridge, MN, Yang, X-J, Gingras, M-C, Gibbs, RA, Rosenblatt, DS, Majewski, J, Lee, BH
JournalAm J Hum Genet
Date Published2012 Feb 10
KeywordsAbnormalities, Multiple, Animals, Blepharophimosis, Blepharoptosis, Bone Diseases, Developmental, Cerebellum, Epigenomics, Exome, Female, Heart Defects, Congenital, Heterozygote, Histone Acetyltransferases, Humans, Intellectual Disability, Male, Mice, Mice, Inbred C57BL, Musculoskeletal Abnormalities, Mutation, Phenotype, Rubinstein-Taybi Syndrome, Sequence Analysis, DNA, Urogenital Abnormalities

Genitopatellar syndrome (GPS) is a skeletal dysplasia with cerebral and genital anomalies for which the molecular basis has not yet been determined. By exome sequencing, we found de novo heterozygous truncating mutations in KAT6B (lysine acetyltransferase 6B, formerly known as MYST4 and MORF) in three subjects; then by Sanger sequencing of KAT6B, we found similar mutations in three additional subjects. The mutant transcripts do not undergo nonsense-mediated decay in cells from subjects with GPS. In addition, human pathological analyses and mouse expression studies point to systemic roles of KAT6B in controlling organismal growth and development. Myst4 (the mouse orthologous gene) is expressed in mouse tissues corresponding to those affected by GPS. Phenotypic differences and similarities between GPS, the Say-Barber-Biesecker variant of Ohdo syndrome (caused by different mutations of KAT6B), and Rubinstein-Taybi syndrome (caused by mutations in other histone acetyltransferases) are discussed. Together, the data support an epigenetic dysregulation of the limb, brain, and genital developmental programs.

Alternate JournalAm J Hum Genet
PubMed ID22265014
PubMed Central IDPMC3276659
Grant ListF30 MH098571 / MH / NIMH NIH HHS / United States
P01 HD070394 / HD / NICHD NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
/ CAPMC / CIHR / Canada

Similar Publications