Manchester eScholar Services

Supported by The University of Manchester Library

In April 2016 Manchester eScholar was replaced by the University of Manchester’s new Research Information Management System, Pure. In the autumn the University’s research outputs will be available to search and browse via a new Research Portal. Until then the University’s full publication record can be accessed via a temporary portal and the old eScholar content is available to search and browse via this archive.

Whole-exome-sequencing identifies mutations in histone acetyltransferase gene KAT6B in individuals with the Say-Barber-Biesecker variant of Ohdo syndrome.

Clayton-Smith, Jill; O'Sullivan, James; Daly, Sarah; Bhaskar, Sanjeev; Day, Ruth; Anderson, Beverley; Voss, Anne K; Thomas, Tim; Biesecker, Leslie G; Smith, Philip; Fryer, Alan; Chandler, Kate E; Kerr, Bronwyn; Tassabehji, May; Lynch, Sally-Ann; Krajewska-Walasek, Malgorzata; McKee, Shane; Smith, Janine; Sweeney, Elizabeth; Mansour, Sahar; Mohammed, Shehla; Donnai, Dian; Black, Graeme

American Journal of Human Genetics. 2011;89(5):675.

Access to files

Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:

Full-text held externally

Abstract

Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS or Ohdo syndrome) is a multiple anomaly syndrome characterized by severe intellectual disability, blepharophimosis, and a mask-like facial appearance. A number of individuals with SBBYSS also have thyroid abnormalities and cleft palate. The condition usually occurs sporadically and is therefore presumed to be due in most cases to new dominant mutations. In individuals with SBBYSS, a whole-exome sequencing approach was used to demonstrate de novo protein-truncating mutations in the highly conserved histone acetyltransferase gene KAT6B (MYST4/MORF)) in three out of four individuals sequenced. Sanger sequencing was used to confirm truncating mutations of KAT6B, clustering in the final exon of the gene in all four individuals and in a further nine persons with typical SBBYSS. Where parental samples were available, the mutations were shown to have occurred de novo. During mammalian development KAT6B is upregulated specifically in the developing central nervous system, facial structures, and limb buds. The phenotypic features seen in the Qkf mouse, a hypomorphic Kat6b mutant, include small eyes, ventrally placed ears and long first digits that mirror the human phenotype. This is a further example of how perturbation of a protein involved in chromatin modification might give rise to a multisystem developmental disorder.

Bibliographic metadata

Type of resource:
Content type:
Publication type:
Published date:
ISSN:
Place of publication:
United States
Volume:
89
Issue:
5
Start page:
675
Total:
1
Pagination:
675
Digital Object Identifier:
10.1016/j.ajhg.2011.10.008
Pubmed Identifier:
22077973
Pii Identifier:
S0002-9297(11)00442-3
Access state:
Active

Institutional metadata

University researcher(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:144338
Created by:
Black, Graeme
Created:
4th January, 2012, 13:48:59
Last modified by:
Black, Graeme
Last modified:
21st January, 2015, 08:23:38