The OTX2 gene provides instructions for producing a protein that regulates the activity of other genes. On the basis of this action, the OTX2 protein is called a transcription factor. The OTX2 gene is part of a family of homeobox genes, which act during early embryonic development to control the formation of many body structures.
The OTX2 gene plays a critical role in the development of the eyes and related structures, such as the nerves that carry visual information from the eyes to the brain (optic nerves). It is also involved in brain development, including the formation of the pituitary gland at the base of the brain. The pituitary gland produces hormones that help control growth, reproduction, and other critical body functions.
Health Conditions Related to Genetic Changes
At least eight mutations in the OTX2 gene have been identified in people with the major features of septo-optic dysplasia. Some of these mutations prevent the production of a functional OTX2 protein. Other mutations lead to a defective version of the protein that cannot regulate the activity of other genes.
A shortage of the OTX2 protein disrupts the formation and early development of the eyes, the optic nerves, the pituitary gland, and other brain structures. These problems with development lead to the major features of septo-optic dysplasia, including eye abnormalities, underdevelopment of the pituitary gland (pituitary hypoplasia), and learning difficulties. However, the signs and symptoms associated with OTX2 gene mutations vary widely, even among affected members of the same family. Additional features that have been reported in people with OTX2 gene mutations include delayed development, slow growth, and seizures.
Studies suggest that mutations in the OTX2 gene are a rare cause of septo-optic dysplasia.More About This Health Condition
MedlinePlus Genetics provides information about ColobomaMore About This Health Condition
Combined pituitary hormone deficiency
MedlinePlus Genetics provides information about Combined pituitary hormone deficiencyMore About This Health Condition
MedlinePlus Genetics provides information about MicrophthalmiaMore About This Health Condition
Other Names for This Gene
- homeobox protein OTX2
- orthodenticle homolog 2
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Dateki S, Fukami M, Sato N, Muroya K, Adachi M, Ogata T. OTX2 mutation in a patient with anophthalmia, short stature, and partial growth hormone deficiency: functional studies using the IRBP, HESX1, and POU1F1 promoters. J Clin Endocrinol Metab. 2008 Oct;93(10):3697-702. doi: 10.1210/jc.2008-0720. Epub 2008 Jul 15. Citation on PubMed
- Dateki S, Kosaka K, Hasegawa K, Tanaka H, Azuma N, Yokoya S, Muroya K, Adachi M, Tajima T, Motomura K, Kinoshita E, Moriuchi H, Sato N, Fukami M, Ogata T. Heterozygous orthodenticle homeobox 2 mutations are associated with variable pituitary phenotype. J Clin Endocrinol Metab. 2010 Feb;95(2):756-64. doi: 10.1210/jc.2009-1334. Epub 2009 Dec 4. Citation on PubMed
- Diaczok D, Romero C, Zunich J, Marshall I, Radovick S. A novel dominant negative mutation of OTX2 associated with combined pituitary hormone deficiency. J Clin Endocrinol Metab. 2008 Nov;93(11):4351-9. doi: 10.1210/jc.2008-1189. Epub 2008 Aug 26. Citation on PubMed or Free article on PubMed Central
- Ragge NK, Brown AG, Poloschek CM, Lorenz B, Henderson RA, Clarke MP, Russell-Eggitt I, Fielder A, Gerrelli D, Martinez-Barbera JP, Ruddle P, Hurst J, Collin JR, Salt A, Cooper ST, Thompson PJ, Sisodiya SM, Williamson KA, Fitzpatrick DR, van Heyningen V, Hanson IM. Heterozygous mutations of OTX2 cause severe ocular malformations. Am J Hum Genet. 2005 Jun;76(6):1008-22. Epub 2005 Apr 21. Erratum in: Am J Hum Genet. 2005 Aug;77(2):334. Citation on PubMed or Free article on PubMed Central
- Tajima T, Ohtake A, Hoshino M, Amemiya S, Sasaki N, Ishizu K, Fujieda K. OTX2 loss of function mutation causes anophthalmia and combined pituitary hormone deficiency with a small anterior and ectopic posterior pituitary. J Clin Endocrinol Metab. 2009 Jan;94(1):314-9. doi: 10.1210/jc.2008-1219. Epub 2008 Oct 14. Citation on PubMed
- Wyatt A, Bakrania P, Bunyan DJ, Osborne RJ, Crolla JA, Salt A, Ayuso C, Newbury-Ecob R, Abou-Rayyah Y, Collin JR, Robinson D, Ragge N. Novel heterozygous OTX2 mutations and whole gene deletions in anophthalmia, microphthalmia and coloboma. Hum Mutat. 2008 Nov;29(11):E278-83. doi: 10.1002/humu.20869. Citation on PubMed