Holt, R;
Iseri, SAU;
Wyatt, AW;
Bax, DA;
Diaz, DG;
Santos, C;
Broadgate, S;
... Ragge, N; + view all
(2017)
Identification and functional characterisation of genetic variants in OLFM2 in children with developmental eye disorders.
Human Genetics
, 136
(1)
pp. 119-127.
10.1007/s00439-016-1745-8.
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Abstract
Anophthalmia, microphthalmia, and coloboma are a genetically heterogeneous spectrum of developmental eye disorders and affect around 30 per 100,000 live births. OLFM2 encodes a secreted glycoprotein belonging to the noelin family of olfactomedin domain-containing proteins that modulate the timing of neuronal differentiation during development. OLFM2 SNPs have been associated with open angle glaucoma in a case–control study, and knockdown of Olfm2 in zebrafish results in reduced eye size. From a cohort of 258 individuals with developmental eye anomalies, we identified two with heterozygous variants in OLFM2: an individual with bilateral microphthalmia carrying a de novo 19p13.2 microdeletion involving OLFM2 and a second individual with unilateral microphthalmia and contralateral coloboma who had a novel single base change in the 5′ untranslated region. Dual luciferase assays demonstrated that the latter variant causes a significant decrease in expression of OLFM2. Furthermore, RNA in situ hybridisation experiments using human developmental tissue revealed expression in relevant structures, including the lens vesicle and optic cup. Our study indicates that OLFM2 is likely to be important in mammalian eye development and disease and should be considered as a gene for human ocular anomalies.
| Type: | Article |
|---|---|
| Title: | Identification and functional characterisation of genetic variants in OLFM2 in children with developmental eye disorders |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s00439-016-1745-8 |
| Publisher version: | http://doi.org/10.1007/s00439-016-1745-8 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1541349 |
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