Skip Navigation


Human Molecular Genetics Advance Access originally published online on March 16, 2006
Human Molecular Genetics 2006 15(9):1413-1422; doi:10.1093/hmg/ddl064
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Material
Right arrow A corrigendum has been published
Right arrow All Versions of this Article:
15/9/1413    most recent
ddl064v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (36)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Williamson, K. A.
Right arrow Articles by FitzPatrick, D. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Williamson, K. A.
Right arrow Articles by FitzPatrick, D. R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome

Kathleen A. Williamson1, Ann M. Hever1, Joe Rainger1, R. Curtis Rogers4, Alex Magee2, Zdenek Fiedler3, Wee Teik Keng1, Freddie H. Sharkey1, Niolette McGill1, Clare J. Hill5, Adele Schneider6, Mario Messina7, Peter D. Turnpenny8, Judy A. Fantes1, Veronica van Heyningen1 and David R. FitzPatrick1,*

1Medical Genetics Section, MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK, 2Regional Genetics Service A Floor, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, UK, 3Department of Biological and Biochemical Sciences, University Pardubice, Czech Republic, 4Greenwood Genetic Center, 1 Gregor Mendel Circle, Greenwood, South Carolina 29646, USA, 5Institute of Medical Genetics, University Hospital of Wales, Cardiff CF14 4XW, UK, 6Department of Clinical Genetics, Albert Einstein Medical Center, Philadelphia, PA, USA, 7Section of Pediatric Surgery, Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Italy and 8Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK

* To whom correspondence should be addressed. Tel: +44 1313322471; Fax: +44 1314678456; Email: david.fitzpatrick{at}hgu.mrc.ac.uk

Received December 23, 2005; Accepted March 10, 2006

We report heterozygous, loss-of-function SOX2 mutations in three unrelated individuals with Anophthalmia-Esophageal-Genital (AEG) syndrome. One previously reported case [Rogers, R.C. (1988) Unknown cases. Proceedings of the Greenwood Genetic Center. 7, 57.] has a 2.7 Mb deletion encompassing SOX2 and associated with a cryptic translocation t(3;7)(q28;p21.3). The deletion and translocation breakpoints on chromosome 3q are >8.6 Mb apart and both chromosome rearrangements have occurred de novo. Another published case [Petrackova et al. (2004) Association of oesophageal atresia, anophthalmia and renal duplex. Eur. J. Pediatr., 163, 333–334.] has a de novo nonsense mutation, Q55X. A previously unreported case with severe bilateral microphthalmia and oesophageal atresia has a de novo missense mutation, R74P, that alters a highly evolutionarily conserved residue within the high mobility group domain, which is critical for DNA-binding of SOX2. In a yeast one-hybrid assay, this mutation abolishes Sox2-induced activation of the chick delta-crystallin DC5 enhancer. Four other reported AEG syndrome cases were extensively screened and do not have detectable SOX2 mutations. Two of these cases have unilateral eye malformations. SOX2 mutations are known to cause severe bilateral eye malformations but this is the first report implicating loss of function mutations in this transcription factor in oesophageal malformations. SOX2 is expressed in the developing foregut in mouse and zebrafish embryos and an apparently normal pattern of expression is maintained in Shh–/– mouse embryos, suggesting either that Sox2 acts upstream of Shh or functions in a different pathway. Three-dimensional reconstructions of the major morphological events in the developing foregut and eye from Carnegie Stages 12 and 13 human embryos are presented and compared with the data from model organisms. SOX2, with NMYC and CHD7, is now the third transcriptional regulator known to be critical for normal oesophageal development in humans.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 DevelopmentHome page
R. R. Driskell, A. Giangreco, K. B. Jensen, K. W. Mulder, and F. M. Watt
Sox2-positive dermal papilla cells specify hair follicle type in mammalian epidermis
Development, August 15, 2009; 136(16): 2815 - 2823.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
C. Gontan, T. Guttler, E. Engelen, J. Demmers, M. Fornerod, F. G. Grosveld, D. Tibboel, D. Gorlich, R. A. Poot, and R. J. Rottier
Exportin 4 mediates a novel nuclear import pathway for Sox family transcription factors
J. Cell Biol., April 6, 2009; 185(1): 27 - 34.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
K. S Alatzoglou, D. Kelberman, and M. T Dattani
The role of SOX proteins in normal pituitary development
J. Endocrinol., March 1, 2009; 200(3): 245 - 258.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
D. Kelberman, S. C. P. de Castro, S. Huang, J. A. Crolla, R. Palmer, J. W. Gregory, D. Taylor, L. Cavallo, M. F. Faienza, R. Fischetto, et al.
SOX2 Plays a Critical Role in the Pituitary, Forebrain, and Eye during Human Embryonic Development
J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1865 - 1873.
[Abstract] [Full Text] [PDF]

Home page
 Arch OphthalmolHome page
P. Wang, X. Liang, J. Yi, and Q. Zhang
Novel SOX2 Mutation Associated With Ocular Coloboma in a Chinese Family
Arch Ophthalmol, May 1, 2008; 126(5): 709 - 713.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. Danno, T. Michiue, K. Hitachi, A. Yukita, S. Ishiura, and M. Asashima
Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression
PNAS, April 8, 2008; 105(14): 5408 - 5413.
[Abstract] [Full Text] [PDF]

Home page
 Br J OphthalmolHome page
P Bakrania, D O Robinson, D J Bunyan, A Salt, A Martin, J A Crolla, A Wyatt, A Fielder, J Ainsworth, A Moore, et al.
SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions
Br J Ophthalmol, November 1, 2007; 91(11): 1471 - 1476.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
D. Kelberman and M. T. Dattani
Hypothalamic and pituitary development: novel insights into the aetiology
Eur. J. Endocrinol., August 1, 2007; 157(suppl_1): S3 - S14.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
J. Que, T. Okubo, J. R. Goldenring, K.-T. Nam, R. Kurotani, E. E. Morrisey, O. Taranova, L. H. Pevny, and B. L. M. Hogan
Multiple dose-dependent roles for Sox2 in the patterning and differentiation of anterior foregut endoderm
Development, July 1, 2007; 134(13): 2521 - 2531.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
N. Sato, Y. Kamachi, H. Kondoh, Y. Shima, K.-i. Morohashi, R. Horikawa, and T. Ogata
Hypogonadotropic hypogonadism in an adult female with a heterozygous hypomorphic mutation of SOX2
Eur. J. Endocrinol., February 1, 2007; 156(2): 167 - 171.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
T. Okubo, L. H. Pevny, and B. L.M. Hogan
Sox2 is required for development of taste bud sensory cells
Genes & Dev., October 1, 2006; 20(19): 2654 - 2659.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.