The University of Southampton
University of Southampton Institutional Repository

SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions

SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions
SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions
BACKGROUND: Developmental eye anomalies, which include anophthalmia (absent eye) or microphthalmia (small eye) are an important cause of severe visual impairment in infants and young children. Heterozygous mutations in SOX2, a SOX1B-HMG box transcription factor, have been found in up to 10% of individuals with severe microphthalmia or anophthalmia and such mutations could also be associated with a range of non-ocular abnormalities. METHODS: We performed mutation analysis on a new cohort of 120 patients with congenital eye abnormalities, mainly anophthalmia, microphthalmia and coloboma. Multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridisation (FISH) were used to detect whole gene deletion. RESULTS: We identified four novel intragenic SOX2 mutations (one single base deletion, one single base duplication and two point mutations generating premature translational termination codons) and two further cases with the previously reported c.70del20 mutation. Of 52 patients with severe microphthalmia or anophthalmia analysed by MLPA, 5 were found to be deleted for the whole SOX2 gene and 1 had a partial deletion. In two of these, FISH studies identified sub-microscopic deletions involving a minimum of 328 Kb and 550 Kb. The SOX2 phenotypes include a patient with anophthalmia, oesophageal abnormalities and horseshoe kidney, and a patient with a retinal dystrophy implicating SOX2 in retinal development. CONCLUSION: Our results provide further evidence that SOX2 haploinsufficiency is a common cause of severe developmental ocular malformations and that background genetic variation determines the varying phenotypes. Given the high incidence of whole gene deletion we recommend that all patients with severe microphthalmia or anophthalmia, including unilateral cases be screened by MLPA and FISH for SOX2 deletions
phenotype, fluorescence, congenital, polymerase chain reaction, cohort, adolescent, DNA mutational analysis, syndrome, anophthalmos, point mutation, research support, codon, eye abnormalities, transcription factors, physiology, microphthalmos, humans, male, multicenter studies, in situ hybridization, genetics, abnormalities, research, middle aged, proteins, patients, adult, methods, protein, infant, child, kidney, mutation, hmgb proteins, gene deletion, analysis, preschool, eye, female, incidence
0007-1161
1471-1476
Bakrania, P.
705c184c-5420-42b1-8311-c9a2ffbc3206
Robinson, D.O.
6b7e8cdc-b9c4-4ecf-a344-1bf0ae990f8a
Bunyan, D.J.
41347b93-e79b-4026-93f9-dd1004cfa05e
Salt, A.
bdb62f4f-2360-4ab1-93a8-975e300ee61c
Martin, A.
169f0afa-12fc-43b5-a72d-7bfc493aa170
Crolla, J.A.
c5f23751-8de9-4a55-9cc5-ca2fb635769c
Wyatt, A.
d5af8f30-69af-4e54-8e7d-e8a086e1860f
Fielder, A.
d16f9fbf-def2-4806-b066-4b45d0254272
Ainsworth, J.
cac9b842-d130-4273-8af5-f3dc63dc6399
Moore, A.
3ef88e9c-073c-4ca3-bf54-ad3ccc4bcc9c
Read, S.
79b01871-5271-4ee4-8991-5e03d1aeab24
Uddin, J.
41f67c1c-ae50-4140-b7d8-fab86a8d1c4f
Laws, D.
66c2fc5c-c733-4be2-a0a7-f44df4cff700
Pascuel-Salcedo, D.
efed3dc9-75f8-4875-bd23-2ecb66d2680a
Ayuso, C.
1b0865b3-fa09-4b71-a9f3-a33c442d6990
Allen, L.
dfec9b60-935b-4061-b010-679ed9a76b54
Collin, J.R.
1a9f7acb-513f-43a3-a57a-4f6e0afacbb6
Ragge, N.K.
a06dd31c-2387-4db0-a3fe-92731ec0724a
Bakrania, P.
705c184c-5420-42b1-8311-c9a2ffbc3206
Robinson, D.O.
6b7e8cdc-b9c4-4ecf-a344-1bf0ae990f8a
Bunyan, D.J.
41347b93-e79b-4026-93f9-dd1004cfa05e
Salt, A.
bdb62f4f-2360-4ab1-93a8-975e300ee61c
Martin, A.
169f0afa-12fc-43b5-a72d-7bfc493aa170
Crolla, J.A.
c5f23751-8de9-4a55-9cc5-ca2fb635769c
Wyatt, A.
d5af8f30-69af-4e54-8e7d-e8a086e1860f
Fielder, A.
d16f9fbf-def2-4806-b066-4b45d0254272
Ainsworth, J.
cac9b842-d130-4273-8af5-f3dc63dc6399
Moore, A.
3ef88e9c-073c-4ca3-bf54-ad3ccc4bcc9c
Read, S.
79b01871-5271-4ee4-8991-5e03d1aeab24
Uddin, J.
41f67c1c-ae50-4140-b7d8-fab86a8d1c4f
Laws, D.
66c2fc5c-c733-4be2-a0a7-f44df4cff700
Pascuel-Salcedo, D.
efed3dc9-75f8-4875-bd23-2ecb66d2680a
Ayuso, C.
1b0865b3-fa09-4b71-a9f3-a33c442d6990
Allen, L.
dfec9b60-935b-4061-b010-679ed9a76b54
Collin, J.R.
1a9f7acb-513f-43a3-a57a-4f6e0afacbb6
Ragge, N.K.
a06dd31c-2387-4db0-a3fe-92731ec0724a

Bakrania, P., Robinson, D.O., Bunyan, D.J., Salt, A., Martin, A., Crolla, J.A., Wyatt, A., Fielder, A., Ainsworth, J., Moore, A., Read, S., Uddin, J., Laws, D., Pascuel-Salcedo, D., Ayuso, C., Allen, L., Collin, J.R. and Ragge, N.K. (2007) SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions. British Journal of Ophthalmology, 91 (11), 1471-1476. (doi:10.1136/bjo.2007.117929).

Record type: Article

Abstract

BACKGROUND: Developmental eye anomalies, which include anophthalmia (absent eye) or microphthalmia (small eye) are an important cause of severe visual impairment in infants and young children. Heterozygous mutations in SOX2, a SOX1B-HMG box transcription factor, have been found in up to 10% of individuals with severe microphthalmia or anophthalmia and such mutations could also be associated with a range of non-ocular abnormalities. METHODS: We performed mutation analysis on a new cohort of 120 patients with congenital eye abnormalities, mainly anophthalmia, microphthalmia and coloboma. Multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridisation (FISH) were used to detect whole gene deletion. RESULTS: We identified four novel intragenic SOX2 mutations (one single base deletion, one single base duplication and two point mutations generating premature translational termination codons) and two further cases with the previously reported c.70del20 mutation. Of 52 patients with severe microphthalmia or anophthalmia analysed by MLPA, 5 were found to be deleted for the whole SOX2 gene and 1 had a partial deletion. In two of these, FISH studies identified sub-microscopic deletions involving a minimum of 328 Kb and 550 Kb. The SOX2 phenotypes include a patient with anophthalmia, oesophageal abnormalities and horseshoe kidney, and a patient with a retinal dystrophy implicating SOX2 in retinal development. CONCLUSION: Our results provide further evidence that SOX2 haploinsufficiency is a common cause of severe developmental ocular malformations and that background genetic variation determines the varying phenotypes. Given the high incidence of whole gene deletion we recommend that all patients with severe microphthalmia or anophthalmia, including unilateral cases be screened by MLPA and FISH for SOX2 deletions

Full text not available from this repository.

More information

Published date: November 2007
Keywords: phenotype, fluorescence, congenital, polymerase chain reaction, cohort, adolescent, DNA mutational analysis, syndrome, anophthalmos, point mutation, research support, codon, eye abnormalities, transcription factors, physiology, microphthalmos, humans, male, multicenter studies, in situ hybridization, genetics, abnormalities, research, middle aged, proteins, patients, adult, methods, protein, infant, child, kidney, mutation, hmgb proteins, gene deletion, analysis, preschool, eye, female, incidence

Identifiers

Local EPrints ID: 59457
URI: https://eprints.soton.ac.uk/id/eprint/59457
ISSN: 0007-1161
PURE UUID: ad479c97-e0d5-49f3-9ec6-e6b579f961aa

Catalogue record

Date deposited: 02 Sep 2008
Last modified: 13 Mar 2019 20:30

Export record

Altmetrics

Contributors

Author: P. Bakrania
Author: D.O. Robinson
Author: D.J. Bunyan
Author: A. Salt
Author: A. Martin
Author: J.A. Crolla
Author: A. Wyatt
Author: A. Fielder
Author: J. Ainsworth
Author: A. Moore
Author: S. Read
Author: J. Uddin
Author: D. Laws
Author: D. Pascuel-Salcedo
Author: C. Ayuso
Author: L. Allen
Author: J.R. Collin
Author: N.K. Ragge

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×