Ragge, N.K and Brown, A. G. and Poloschek, Charlotte M. and Lorenz, Birgit and Henderson, R.A. and Clarke, M. P. and Russell-Eggitt, I. and Fielder, A. and Gerrelli, D. and Martinez-Barbera, J. P. and Ruddle, P. and Hurst, J. and Collin, J. R. O. and Salt, A. and Cooper, S. T. and Thompson, P. J. and Sisodiya, S. M. and Williamson, K. A. and FitzPatrick, D. R. and van Heyningen, V. and Hanson, I.M . (2005) Heterozygous mutations of OTX2 cause severe ocular malformations. AMERICAN JOURNAL OF HUMAN GENETICS, 76 (6). pp. 1008-1022. ISSN 0002-9297, 1537-6605
Full text not available from this repository. (Request a copy)Abstract
Major malformations of the human eye, including microphthalmia and anophthalmia, are examples of phenotypes that recur in families yet often show no clear Mendelian inheritance pattern. Defining loci by mapping is therefore rarely feasible. Using a candidate-gene approach, we have identified heterozygous coding-region changes in the homeobox gene OTX2 in eight families with ocular malformations. The expression pattern of OTX2 in human embryos is consistent with the eye phenotypes observed in the patients, which range from bilateral anophthalmia to retinal defects resembling Leber congenital amaurosis and pigmentary retinopathy. Magnetic resonance imaging scans revealed defects of the optic nerve, optic chiasm, and, in some cases, brain. In two families, the mutations appear to have occurred de novo in severely affected offspring, and, in two other families, the mutations have been inherited from a gonosomal mosaic parent. Data from these four families support a simple model in which OTX2 heterozygous loss-of-function mutations cause ocular malformations. Four additional families display complex inheritance patterns, suggesting that OTX2 mutations alone may not lead to consistent phenotypes. The high incidence of mosaicism and the reduced penetrance have implications for genetic counseling.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LEBER CONGENITAL AMAUROSIS; TRANSCRIPTION-FACTOR; ANTERIOR NEUROECTODERM; RETINITIS-PIGMENTOSA; HOMEOBOX GENE; NEURAL RETINA; EXPRESSION; EYE; PHOTORECEPTOR; SPECIFICATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Pädiatrische Ophthalmologie, Strabismologie und Ophthalmogenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 May 2021 09:29 |
| Last Modified: | 10 May 2021 09:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/36015 |
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