Normal Function
The USH2A gene provides instructions for making a protein called usherin. Usherin is an important component of basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues. Usherin is found in basement membranes in the inner ear and in the retina, which is the layer of light-sensitive tissue at the back of the eye. Although the function of usherin has not been well established, studies suggest that it is part of a group of proteins (a protein complex) that plays an important role in the development and maintenance of cells in the inner ear and retina. The protein complex may also be involved in the function of synapses, which are junctions between nerve cells where cell-to-cell communication occurs.
Health Conditions Related to Genetic Changes
Retinitis pigmentosa
Several dozen mutations in the USH2A gene have been reported to cause retinitis pigmentosa, a vision disorder that causes the light-sensing cells of the retina to gradually deteriorate. USH2A gene mutations are the most common cause of the autosomal recessive form of retinitis pigmentosa, accounting for 10 to 15 percent of all cases. This form of the disorder is described as nonsyndromic, which means that it is not associated with other signs and symptoms as part of a genetic syndrome (such as Usher syndrome, described below).
The USH2A gene mutations that cause retinitis pigmentosa change single protein building blocks (amino acids) in the usherin protein. Through a mechanism that is not well understood, these genetic changes lead to the gradual breakdown of specialized light receptor cells called photoreceptors in the retina. A loss of these cells underlies the progressive vision loss characteristic of this condition.
More About This Health ConditionUsher syndrome
More than 400 mutations in the USH2A gene have been identified in people with Usher syndrome type II, which is characterized by a combination of hearing loss and vision loss associated with retinitis pigmentosa. Specifically, USH2A gene mutations cause a form of the disorder known as Usher syndrome type IIA (USH2A), which accounts for more than half of all cases of Usher syndrome type II.
Several of these mutations change single amino acids in the usherin protein. These mutations often lead to the production of an abnormally short version of the protein or prevent the cell from making any functional usherin. Other mutations insert or delete small amounts of DNA in the USH2A gene, which probably impairs the normal function of usherin. Researchers have not determined how a missing or altered usherin protein leads to the hearing impairment and vision loss that are characteristic of Usher syndrome type IIA.
It is unclear why some USH2A gene mutations result in Usher syndrome type IIA, while other mutations cause retinitis pigmentosa without hearing loss.
More About This Health ConditionOther Names for This Gene
- US2
- USH2
- USH2A_HUMAN
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Adato A, Lefevre G, Delprat B, Michel V, Michalski N, Chardenoux S, Weil D, El-Amraoui A, Petit C. Usherin, the defective protein in Usher syndrome type IIA, is likely to be a component of interstereocilia ankle links in the inner ear sensory cells. Hum Mol Genet. 2005 Dec 15;14(24):3921-32. doi: 10.1093/hmg/ddi416. Epub 2005 Nov 21. Citation on PubMed
- Bhattacharya G, Miller C, Kimberling WJ, Jablonski MM, Cosgrove D. Localization and expression of usherin: a novel basement membrane protein defective in people with Usher's syndrome type IIa. Hear Res. 2002 Jan;163(1-2):1-11. doi: 10.1016/s0378-5955(01)00344-6. Citation on PubMed
- Blanco-Kelly F, Jaijo T, Aller E, Avila-Fernandez A, Lopez-Molina MI, Gimenez A, Garcia-Sandoval B, Millan JM, Ayuso C. Clinical aspects of Usher syndrome and the USH2A gene in a cohort of 433 patients. JAMA Ophthalmol. 2015 Feb;133(2):157-64. doi: 10.1001/jamaophthalmol.2014.4498. Citation on PubMed
- Chen X, Sheng X, Liu X, Li H, Liu Y, Rong W, Ha S, Liu W, Kang X, Zhao K, Zhao C. Targeted next-generation sequencing reveals novel USH2A mutations associated with diverse disease phenotypes: implications for clinical and molecular diagnosis. PLoS One. 2014 Aug 18;9(8):e105439. doi: 10.1371/journal.pone.0105439. eCollection 2014. Citation on PubMed or Free article on PubMed Central
- Liu X, Bulgakov OV, Darrow KN, Pawlyk B, Adamian M, Liberman MC, Li T. Usherin is required for maintenance of retinal photoreceptors and normal development of cochlear hair cells. Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4413-8. doi: 10.1073/pnas.0610950104. Epub 2007 Mar 5. Citation on PubMed or Free article on PubMed Central
- McGee TL, Seyedahmadi BJ, Sweeney MO, Dryja TP, Berson EL. Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa. J Med Genet. 2010 Jul;47(7):499-506. doi: 10.1136/jmg.2009.075143. Epub 2010 May 27. Citation on PubMed or Free article on PubMed Central
- Sandberg MA, Rosner B, Weigel-DiFranco C, McGee TL, Dryja TP, Berson EL. Disease course in patients with autosomal recessive retinitis pigmentosa due to the USH2A gene. Invest Ophthalmol Vis Sci. 2008 Dec;49(12):5532-9. doi: 10.1167/iovs.08-2009. Epub 2008 Jul 18. Citation on PubMed or Free article on PubMed Central
- van Wijk E, Pennings RJ, te Brinke H, Claassen A, Yntema HG, Hoefsloot LH, Cremers FP, Cremers CW, Kremer H. Identification of 51 novel exons of the Usher syndrome type 2A (USH2A) gene that encode multiple conserved functional domains and that are mutated in patients with Usher syndrome type II. Am J Hum Genet. 2004 Apr;74(4):738-44. doi: 10.1086/383096. Epub 2004 Mar 10. Citation on PubMed or Free article on PubMed Central
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