Usher syndrome
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2008-07-03T16:30:56Z
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{{Infobox_Disease |
Name = Usher syndrome |
Image = |
Caption = |
DiseasesDB = 13611 |
ICD10 = |
ICD9 = |
ICDO = |
OMIM = 276900 |
OMIM_mult = {{OMIM2|276901}} |
MedlinePlus = |
eMedicineSubj = |
eMedicineTopic = |
MeshID = D052245 |
}}
A leading cause of [[deaf-blindness]], '''Usher syndrome''' (sometimes referred to as "'''Usher's syndrome'''") is a relatively rare [[genetic disorder]] that is associated with a mutation in any one of 10 [[gene]]s. Other names for Usher syndrome include '''Hallgren syndrome''', '''Usher-Hallgren syndrome''', '''[[retinitis pigmentosa|rp]]-dysacusis syndrome''' and '''dystrophia retinae dysacusis syndrome'''.<ref name="mets_2000" >{{cite journal | author = Mets MB, Young NM, Pass A, Lasky JB | date = 2000 | title = Early diagnosis of Usher syndrome in children | journal = Transactions of the American Ophthalmological Society | volume = 98 | pages = 237–245 | pmid = 11190026}}</ref> Usher syndrome is incurable at present; however, using [[gene therapy]] to replace the missing gene, researchers have succeeded in reversing one form of the disease in [[knockout mouse|knockout mice]].<ref name="hashimoto_2007" />
This [[syndrome]] is characterized by [[deafness]] and a gradual vision loss. The hearing loss is associated with a defective [[inner ear]], whereas the vision loss is associated with [[retinitis pigmentosa]] (rp), a degeneration of the retinal cells. Usually, the [[rod cell]]s of the [[retina]] are affected first, leading to early [[night blindness]] and the gradual loss of [[peripheral vision]]. In other cases, there is early degeneration of the [[cone cell]]s in the [[macula]], leading to a loss of [[visual acuity|central acuity]]. In some cases, the [[fovea]]l vision is spared, leading to "doughnut vision"; central and peripheral vision are intact, but there is an [[annulus (mathematics)|annulus]] around the central region in which [[visual impairment|vision is impaired]].
Usher syndrome has three clinical subtypes, denoted as I, II and III in decreasing order of severity.<ref name="williams_2007">{{cite journal | author = Williams DS | date = 2007 | title = Usher syndrome: Animal models, retinal function of Usher proteins, and prospects for gene therapy | journal = Vision Research | volume = xx | pages = xx–xx | pmid = 17936325}}</ref> People with Usher I are born profoundly deaf, and begin to lose their [[visual perception|vision]] in the first decade of life. They also exhibit [[balance disorder|balance difficulties]] and learn to walk slowly as children, due to problems in their [[vestibular system]]. People with Usher II are also born deaf, but do not seem to have noticeable problems with balance; they also begin to lose their vision later (in the second decade of life) and may preserve some vision even into middle age. People with Usher syndrome III are not born deaf, but experience a gradual loss of their hearing and vision; they may or may not have balance difficulties.
Usher syndrome I and II are associated with a mutation in any one of six or three different [[gene]]s, respectively, whereas only one mutation has been linked with Usher III. Since Usher syndrome is inherited in an [[autosomal recessive]] pattern, both males and females are equally likely to inherit Usher syndrome. [[Consanguinity]] of the parents is a risk factor. Since Usher syndrome mutations are recessive, if both parents have Usher syndrome in the same gene, all their children are overwhelmingly likely to have the same condition; by contrast, the children of a mixed marriage (one parent with Usher syndrome and the other with wild-type genes) are overwhelmingly likely to ''not'' have the condition, although they will be all [[Genetic carrier|carrier]]s. First recognized in the 19th century, Usher syndrome was the first condition to demonstrate that [[phenotype]]s could be inherited in tandem; [[deafness]] and [[blindness]] are inherited together, but not separately. Animal models of this human disease (such as [[knockout mouse|knockout mice]] and [[zebrafish]]) have been developed recently to study the effects of these gene mutations and to test potential cures for Usher syndrome.
== History ==
Usher syndrome is named after the British ophthalmologist [[Charles Usher]], who examined the [[pathology]] and [[transmission]] of this illness in 1914 on the basis of 69 cases.<ref name="Usher">{{cite journal | author = Usher C | date = 1914 | title = On the inheritance of Retinitis pigmentosa with notes of cases | journal = Roy. Lond. Ophthalmol. Hosp. Rep. | volume = 19 | pages = 130–236}}</ref> However, it was first described in 1858 by [[Albrecht von Gräfe]], a pioneer of modern [[ophthalmology]].<ref name="Graefe">{{cite journal | author = von Gräfe A | date = 1858 | title = Exceptionelles Verhalten des Gesichtsfeldes bei Pigmententartung der Netzhaut | journal = Archiv für Ophthalmologie | volume = 4 | pages = 250–253}}</ref> He reported the case of a deaf patient with [[retinitis pigmentosa]], who had two brothers with the same symptoms. Three years later, one of his students, [[Richard Liebreich]], examined the population of Berlin for disease pattern of deafness with retinitis pigmentosa.<ref name="Liebreich">{{ cite journal | author = Liebreich R | date = 1861 | title = Abkunft aus Ehen unter Blutsverwandten als Grund von Retinitis pigmentosa | journal = Dtsch. Klin. | volume = 13 | pages = 53}}</ref> Liebreich noted that Usher syndrome is recessive, since the cases of blind-deafness combinations occurred particularly in the siblings of blood-related marriages or in families with patients in different generations. His observations supplied the first proofs for the coupled transmission of blindness and deafness, since no isolated cases of either could be found in the family trees.
== Symptoms and subtypes ==
[[Image:Autorecessive.jpg|thumb|right|300px|Usher syndrome is inherited in an [[autosomal recessive]] pattern. The genes implicated in Usher syndrome are described below.]]
Usher syndrome is responsible for the majority of [[deaf-blindness]].<ref>{{cite journal | author = Vernon M | date = 1969 | title = Usher's syndrome — deafness and progressive blindness. Clinical cases, prevention, theory and literature survey | journal = Journal of Chronic Disorders | volume = 22 | pages = 133–151 | pmid = 4897966 | doi = 10.1016/0021-9681(69)90055-1}}</ref> The word ''[[syndrome]]'' means that multiple symptoms occur together, in this case, deafness and blindness. It occurs in roughly 1 person in 23,000 in the [[United States]],<ref>{{cite journal | author = Boughman J, Vernon M, Shaver K | date = 1983 | title = Usher syndrome: Definition and estimate of prevalence from two high-risk populations | journal = Journal of Chronic Disorders | volume = 36 | pages = 595–603 | pmid = 6885960 | doi = 10.1016/0021-9681(83)90147-9}}</ref> 1 in 28,000 in Norway<ref>{{cite journal | author = Grøndahl J | date = 1987 | title = Estimation of prognosis and prevalence of retinitis pigmentosa and Usher syndrome in Norway | journal = Clin. Genet. | volume = 31 | pages = 255–264 | pmid = 3594933}}</ref> and 1 in 12,500 in Germany.<ref>{{cite journal | author = Otterstedde CR, Spandau U, Blankenagel A, Kimberling WJ, Reisser C | date = 2001 | title = A new clinical classication for Usher's syndrome based on a new subtype of Usher's syndrome type I | journal = Laryngoscope | volume = 111 | pages = 84–86 | pmid = 11192904 | doi = 10.1097/00005537-200101000-00014}}</ref> People with Usher syndrome represent roughly one-sixth of people with [[retinitis pigmentosa]].<ref name="williams_2007" />
Usher syndrome is inherited in an [[autosomal recessive]] pattern. "Recessive" means that both parents must contribute an appropriate [[gene]] for the syndrome to appear, and "autosomal" means that the gene is ''not'' carried on one of the [[XY sex-determination system|sex chromosome]]s (X or Y), but rather on one of the 22 other pairs. (See the article on [[human genetics]] for more details.)
The progressive blindness of Usher syndrome results from [[retinitis pigmentosa]].<ref name="smith_1994" /><ref>{{cite journal | author = Fishman GA, Kumar A, Joseph ME, Torok N, and Andersonj RJ | fate = 1983 | title = Usher's syndrome | journal = Archives of Ophthalmology |volume = 109 | pages = 1367–1374 | pmid = 6604514}}</ref> The [[photoreceptors]] usually start to degenerate from the outer [[periphery]] to the center of the [[retina]] including the [[macula]]. The degeneration is usually first noticed as [[night blindness]] ([[nyctalopia]]); peripheral vision is gradually lost, restricting the visual field ([[tunnel vision]]), which generally progresses to complete blindness. The qualifier ''pigmentosa'' reflects the fact that clumps of pigment may be visible by an [[ophthalmoscope]] in advanced stages of degeneration.<ref name="williams_2007" />
Although Usher syndrome has been classified clinically in several ways,<ref>
{{cite journal | author = Hammerschlag V | date = 1907 | title = Zur Kenntnis der hereditaer-degenerativen Taubstummen und ihre differential diagnostische Bedeutung | journal = Z. Ohrenheilk. | volume = 54 | pages = 18–36}}<br />
{{cite book | author = Bell J | date = 1933 | title = Retinitis Pigmentosa and Allied Diseases | edition = 2nd edition | publisher = Cambridge University Press | location = London }}<br />
{{cite journal | author = Hallgren B | date = 1959 | title = Retinitis pigmentosa combined with congenital deafness with vestibulo-cerebellar ataxia and mental abnormality in a proportion of cases: Clinical and geneto-statistical survey | journal = [[Acta Psychiatrica Scandinavica]] Suppl. | volume = 138 | pages = 9–101 | pmid = 14399116 }}<br />
{{cite journal | author = Merin S, Auerbach E | date = 1976 | title = Retinitis pigmentosa | journal = Surv. Ophthalmol. | volume = 20 | pages = 303–345 | pmid = 817406 | doi = 10.1016/S0039-6257(96)90001-6}}<br />
{{cite book | author = Davenport S, Omenn G | date = 1977 | title = The Heterogeneity of Usher Syndrome | edition = volume 426 | publisher = Excerpta Medica Foundation | location = Amsterdam }}<br />
{{cite journal | author = Gorlin R, Tilsner T, Feinstein S, Duvall AJ | date = 1979 | title = Usher syndrome type III | journal = Arch. Otolaryngol. | volume = 105 | pages = 353–354 | pmid = 454290}}<br />
{{cite journal | author = Fishman G, Kumar A, Joseph ME, Torok N, Anderson RJ | date = 1983 | title = Usher's syndrome: Ophthalmic and neuro-otologic findings suggesting congenital heterogeneity | journal = Arch. Ophthalmol. | volume = 101 | pages = 1367–1374 | pmid = 6604514}}<br />
{{cite journal | author = Sankila EM, Pakarinen H, Kääriäinen H, Aittomäki K, Karjalainen S, Sistonen P, de la Chapelle A | date = 1995 | title = Assignment of Usher syndrome type III (USH3) gene to chromosome 3q | journal = Hum. Mol. Genetics | volume = 4 | pages = 93–98 | pmid = 7711740}}</ref> the prevailing approach is to classify it into three clinical sub-types called Usher I, II and III in order of decreasing severity of deafness.<ref name="smith_1994" >{{cite journal | author = Smith RJ, Berlin CI, Hejtmancik JF, Keats BJ, Kimberling WJ, Lewis RA, ''et al.'' | date = 1994 | title = Clinical diagnosis of the Usher syndromes. Usher Syndrome Consortium | journal = American Journal of Medical Genetics | volume = 50 | pages = 32–38 | pmid = 8160750 | doi = 10.1002/ajmg.1320500107}}</ref> Usher I and II are the more common forms; the fraction of people with Usher III is significant only in a few specific areas, such as [[Finland]]<ref>{{cite journal | author = Pakarinen L, Tuppurainen K, Laipapala P, Mäntyjärvi M, Puhakka H | date = 1996 | title = The ophthalmological course of Usher syndrome type III | journal = International Ophthalmology | volume = 19 | pages = 307–311 | pmid = 8864816 | doi = 10.1007/BF00130927}}</ref> and [[Birmingham]].<ref>{{cite journal | author = Hope CI, Bundey S, Proops D, Fielder AR | date = 1997 | title = Usher syndrome in the city of Birmingham — prevalence and clinical classification | journal = British Journal of Ophthalmology | volume = 81 | pages = 46–53 | pmid = 9135408}}</ref> As described below, these clinical subtypes may be further subdivided by the particular gene mutated; people with Usher I and II may have any one of six and three genes mutated, respectively, whereas only one gene has been associated with Usher III. The function of these genes is poorly understood as of yet. The hearing impairment associated with Usher syndrome is better understood: damaged hair cells in the [[cochlea]] of the [[inner ear]] inhibit electrical impulses from reaching the brain.
===Usher syndrome I===
People with Usher I are usually born deaf and often have [[balance disorder|difficulties in maintaining their balance]] owing to problems in the [[vestibular system]]. Babies with Usher I are usually slow to develop motor skills such as walking. Worldwide, the estimated prevalence of Usher syndrome type I is 3 to 6 per 100,000 people in the general population.
Usher syndrome type I can be caused by mutations in any one of several different genes: [[CDH23]], [[MYO7A]], [[PCDH15]], [[USH1C]], and [[USH1G]]. These genes function in the development and maintenance of [[inner ear]] structures such as [[hair cell]]s ([[stereocilia]]), which transmit [[sound]] and [[motion (physics)|motion]] signals to the [[brain]]. Alterations in these genes can cause an inability to maintain balance (vestibular dysfunction) and hearing loss. The genes also play a role in the development and stability of the [[retina]] by influencing the structure and function of both the rod photoreceptor cells and supporting cells called the [[retinal pigmented epithelium]]. Mutations that affect the normal function of these genes can result in [[retinitis pigmentosa]] and vision loss.
===Usher syndrome II===
People with Usher II are generally [[hard-of-hearing]] rather than deaf, and their hearing does not degrade over time; moreover, they generally have a normal vestibular system. Usher syndrome type II occurs at least as frequently as type I, but because type II may be underdiagnosed or more difficult to detect, it could be up to three times as common as type I.
Usher syndrome type II may be caused by mutations in any of three different genes: [[USH2A]], [[GPR98]] and [[DFNB31]]. The protein encoded by the USH2A gene, usherin, is located in the supportive tissue in the [[inner ear]] and [[retina]]. Usherin is critical for the proper development and maintenance of these structures, which may help explain its role in hearing and vision loss. The location and function of the other two proteins are not yet known.
===Usher syndrome III===
By contrast, people with Usher III experience a ''progressive'' loss of hearing and roughly half have vestibular dysfunction. The frequency of Usher syndrome type III is highest in the [[Finland|Finnish population]], but it has been noted rarely in a few other ethnic groups.
Mutations in only one gene, the [[CLRN1]] gene, have been linked to Usher syndrome type III. The CLRN1 gene encodes Clarin-1, a protein that is important for the development and maintenance of the inner ear and retina. However, the protein's function in these structures, and how its mutation causes hearing and vision loss, is poorly understood as yet.
==Differential diagnosis==
Since Usher syndrome is incurable at present, it is helpful to diagnose children well before they develop the characteristic night blindness. Some preliminary studies have suggested that as many as 10% of congenitally deaf children may have Usher syndrome.<ref name="mets_2000" /> However, a mis-diagnosis can have bad consequences, e.g., if the parents elect to give the child [[cochlear implant]]s.
The simplest approach to diagnosing Usher syndrome is to test for the characteristic [[chromosom]]al mutations. An alternative approach is [[electroretinography]] (ERG), although this is often disfavored for children, since its discomfort can also make the results unreliable.<ref name="mets_2000" /> Parental consanguinity is a significant factor in diagnosis. Usher syndrome I may be indicated if the child is profoundly deaf from birth and especially slow in walking.
Thirteen other syndromes may exhibit signs similar to Usher syndrome, including [[Alport syndrome]], [[Alstrom syndrome]], [[Bardet-Biedl syndrome]], [[Cockayne syndrome]], [[spondyloepiphyseal dysplasia congenita]], [[Flynn-Aird syndrome]], [[Friedreich ataxia]], [[Hurler syndrome]] (MPS-1), [[Kearns-Sayre syndrome]] (CPEO), [[Norrie syndrome]], [[osteopetrosis]] (Albers-Schonberg disease), [[Refsum's disease]] (phytanic acid storage disease), and [[Zellweger syndrome]] (cerebro-hepato-renal syndrome).
==Genes associated with Usher syndrome==
{| align="right" style="margin-left:1em"
|+ Table 1: Genes linked to Usher syndrome
|----- bgcolor=#CFCFCF
!Type
!Freq <ref>{{cite journal | author = Roux AF, Faugere V, Le Guedard S, Pallares-Ruiz N, Vielle A, Chambert S, Marlin S, Hamel C, Gilbert B, Malcolm S, Claustres M | date = 2006 | title = Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90% | journal = J Med Genet | volume = 43 | pages = 763–768 | pmid = 16679490 | url = http://jmg.bmj.com/cgi/reprint/43/9/763 | doi = 10.1136/jmg.2006.041954}}<br />{{cite journal | author = Ouyang XM, Yan D, Du LL, Hejtmancik JF, Jacobson SG, Nance WE, Li AR, Angeli S, Kaiser M, Newton V, Brown SD, Balkany T, Liu XZ | date = 2005 | title = Characterization of Usher syndrome type I gene mutations in an Usher syndrome patient population | journal = Hum Genet |volume = 116 | pages = 292–299 | pmid = 15660226 | url = http://www.springerlink.com/content/npfkn86hf0fu6q28/ | doi = 10.1007/s00439-004-1227-2}}</ref>
!Gene locus
!Gene
!Protein
!Function
!Size (AA)
!UniProt
![[OMIM]]
|-
|----- bgcolor=#EECCCC
|valign="middle" align="center"|USH1B
|valign="middle" align="center"|39–55%
|[[Chromosome 11|11]]q13.5
|valign="middle" align="center"|[[MYO7A]]
|valign="middle" align="center"|[[Myosin]] VIIA
|valign="middle" align="center"|[[Motor protein]]
|valign="middle" align="center"|2215
|valign="middle" align="center"|{{uniprot|Q13402}}
|valign="middle" align="center"|{{OMIM2|276900}}
|-
|----- bgcolor=#EECCCC
|valign="middle" align="center"|USH1C
|valign="middle" align="center"|6–7%
|[[Chromosome 11|11]]p15.1-p14
|valign="middle" align="center"|[[USH1C]]
|valign="middle" align="center"|[[Usher 1C|Harmonin]]
|valign="middle" align="center"|[[PDZ domain|PDZ-domain protein]]
|valign="middle" align="center"|552
|valign="middle" align="center"|{{uniprot|Q9Y6N9}}
|valign="middle" align="center"|{{OMIM2|276904}}
|-
|----- bgcolor=#EECCCC
|valign="middle" align="center"|USH1D
|valign="middle" align="center"|19–35%
|[[Chromosome 10|10]]q21-q22
|valign="middle" align="center"|[[CDH23]]
|valign="middle" align="center"|[[Cadherin|Cadherin 23]]
|valign="middle" align="center"|[[Cell adhesion]]
|valign="middle" align="center"|3354
|valign="middle" align="center"|{{uniprot|Q9H251}}
|valign="middle" align="center"|{{OMIM2|601067}}
|-
|----- bgcolor=#EECCCC
|valign="middle" align="center"|USH1E
|valign="middle" align="center"|rare
|[[Chromosome 21|21]]q21
|valign="middle" align="center"|?
|valign="middle" align="center"|?
|valign="middle" align="center"|?
|valign="middle" align="center"|?
|valign="middle" align="center"|?
|valign="middle" align="center"|{{OMIM2|602097}}
|-
|----- bgcolor=#EECCCC
|valign="middle" align="center"|USH1F
|valign="middle" align="center"|11–19%
|valign="middle" align="center"|[[Chromosome 10|10]]q11.2-q21
|valign="middle" align="center"|[[PCDH15]]
|valign="middle" align="center"|[[Cadherin|Protocadherin 15]]
|valign="middle" align="center"|[[Cell adhesion]]
|valign="middle" align="center"|1955
|valign="middle" align="center"|{{uniprot|Q96QU1}}
|valign="middle" align="center"|{{OMIM2|602083}}
|-
|----- bgcolor=#EECCCC
|valign="middle" align="center"|USH1G
|valign="middle" align="center"|7%
|[[Chromosome 17|17]]q24-q25
|valign="middle" align="center"|[[USH1G]]
|valign="middle" align="center"|SANS
|valign="middle" align="center"|[[Scaffold protein]]
|valign="middle" align="center"|461
|valign="middle" align="center"|{{uniprot|Q495M9}}
|valign="middle" align="center"|{{OMIM2|606943}}
|-
|----- bgcolor=#D1EEEE
|valign="middle" align="center"|USH2A
|valign="middle" align="center"|80%
|[[Chromosome 1|1]]q41
|valign="middle" align="center"|[[USH2A]]
|valign="middle" align="center"|Usherin
|valign="middle" align="center"|Transmembrane linkage
|valign="middle" align="center"|5202
|valign="middle" align="center"|{{uniprot|O75445}}
|valign="middle" align="center"|{{OMIM2|276901}}
|-
|----- bgcolor=#D1EEEE
|valign="middle" align="center"|USH2C
|valign="middle" align="center"|15%
|[[Chromosome 5|5]]q14.3-q21.1
|valign="middle" align="center"|[[GPR98]]
|valign="middle" align="center"|VLGR1b
|valign="middle" align="center"|Very large [[GPCR]]
|valign="middle" align="center"|6307
|valign="middle" align="center"|{{uniprot|Q8WXG9}}
|valign="middle" align="center"|{{OMIM2|605472}}
|-
|----- bgcolor=#D1EEEE
|valign="middle" align="center"|USH2D
|valign="middle" align="center"|5%
|[[Chromosome 9|9]]q32-q34
|valign="middle" align="center"|[[DFNB31]]
|valign="middle" align="center"|Whirlin
|valign="middle" align="center"|[[PDZ domain|PDZ-domain protein]]
|valign="middle" align="center"|907
|valign="middle" align="center"|{{uniprot|Q9P202}}
|valign="middle" align="center"|{{OMIM2|611383}}
|-
|----- bgcolor=#EEEED1
|valign="middle" align="center"|USH3A
|valign="middle" align="center"|100%
|[[Chromosome 3|3]]q21-q25
|valign="middle" align="center"|[[CLRN1]]
|valign="middle" align="center"|Clarin-1
|valign="middle" align="center"|Synaptic shaping
|valign="middle" align="center"|232
|valign="middle" align="center"|{{uniprot|P58418}}
|valign="middle" align="center"|{{OMIM2|276902}}
|}
Several [[gene]]s have been associated with Usher syndrome using [[linkage analysis]] of patient families (Table 1) and [[DNA sequencing]] of the identified [[Locus|loci]].<ref name="Petit">C. Petit: ''Usher syndrome: from genetics to pathogenesis.'' Annu.Rev.Genomics Hum.Genet. 2001 (2): 271-297 PMID 11701652 </ref><ref name="Reiners"> J. Reiners et al.: ''Molecular basis of human Usher syndrome: deciphering the meshes of the Usher protein network provides insights into the pathomechanisms of the Usher disease.'' Exp Eye Res. 2006;83(1):97-119 PMID 16545802</ref> A mutation in any one of these genes is likely to result in Usher syndrome. The clinical subtypes Usher I and II are associated with mutations in any one of six (USH1B-G) and three (USH2A,C-D) genes, respectively, whereas only one gene, [[USH3A]], has been linked to Usher III so far. Two other genes, USH1A and USH2B, were initially associated with Usher syndrome, but USH2B has not been verified and USH1A was incorrectly determined and does not exist.<ref>S. Gerber et al.: '' USH1A: Chronicle of a Slow Death.'' Am J Hum Genet. 2006;78(2):357-9. PMID 16400615 </ref> Research in this area is ongoing.
Using interaction analysis techniques it could be shown that the identified gene products interact with one another in one or more larger [[protein complex]]es. If one of the components is missing, this protein complex cannot fulfill its function in the living [[cell (biology)|cell]] and it probably comes to the [[degeneration]] the same. The function of this protein complex has been suggested to participate in the [[signal transduction]] or in the [[cell adhesion]] of sensory cells.<ref name= "Reiners"/>
==Prospects for gene therapy==
Since Usher syndrome results from the loss of a gene, [[gene therapy]] that adds the proper protein back ("gene replacement") may alleviate it, provided that the added protein becomes functional. Recent studies of [[knockout mouse|mouse models]] have shown that one form of the disease — that associated with a mutation in [[myosin]] VIIa — can be alleviated by [[gene therapy|replacing the mutant gene]] using a [[lentivirus]].<ref name="hashimoto_2007" >{{cite journal | author = Hashimoto T, Gibbs D, Lillo C, Azarian SM, Legacki E, Zhang XM, Yang XJ, Williams DS | date = 2007 | title = Lentiviral gene replacement therapy of retinas in a mouse model for Usher syndrome type 1B | journal = Gene Therapy | volume = 14 | pages = 584–594 | pmid = 17268537 | doi = 10.1038/sj.gt.3302897 | unused_data = |Azarian SM, LegackiE|Zhang XM ''et al.''}}</ref> However, some of the mutated genes associated with Usher syndrome [[Central dogma of molecular biology|encode]] very large [[protein]]s — most notably, the [[USH2A]] and [[GPR98]] [[protein]]s, which have roughly 6000 [[amino acid|amino-acid]] residues. Gene replacement therapy for such large proteins may be difficult.
==Individual cases==
A 28-year-old woman with Usher syndrome, Rebecca Alexander, was profiled in ''[[Marie Claire]]'' in November 2007.<ref>{{cite journal | author = Alexander R, Grossman AJ | date = November 2007 | title = out of sight, out of sound | journal = [[Marie Claire]] | volume = 14 | issue = 11 | pages = 191–193}}</ref> After graduating from the [[University of Michigan]] with excellent marks, Alexander went on [[Columbia University]], where she earned two master's degrees in public health and clinical social work. Today she is a social worker at a school for the deaf, and organizes seminars for the [http://blindness.org Foundation Fighting Blindness]. She is also in private practice as a psychotherapist for eating disorders.
Christine "Coco" Roschaert<ref>[http://tactiletheworld.wordpress.com/ Coco's blog]</ref> is a well-known person with Usher syndrome. She has published video blogs at Youtube,<ref>[http://www.youtube.com/user/tactiletheworld Coco's user page at YouTube]</ref> , and recently was the kick-off speaker for the Deaf Awareness Week at the [[University of Vermont]].<ref>[http://www.uvm.edu/~asl/ ASL at UVM<!-- Bot generated title -->]</ref> In 2006, she graduated with a degree in Communication Sciences from [[Gallaudet University]]; there, she was a hunger striker in the 2006 protest organized by the [[Gallaudet United Now Movement]].<ref>[http://www.xanga.com/tactilejunkie/545143343/item.html First-person account of the 2006 protests at Gallaudet University]</ref> Roschaert is now in [[Nigeria]] founding the first [[deafblind]] program in that country.
A web-community, [http://usher.co.uk UsherLife], of people with Usher syndrome was founded on 1 February 2005 by Nick Sturley. Although centered on [[Great Britain]], it offers resources to all people with Usher syndrome. The organization is hosting regular get-togethers in England, such as the Usher Hood Pub in Nottingham<ref>[http://uk.youtube.com/watch?v=LaOmJBXQo1c First Usher Hood Pub on 21 July 2007 (YouTube)]</ref> and a trip to Brighton pier.<ref>[http://www.youtube.com/watch?v=RjD9sXk05Tg Trip to Brighton Pier on 9 June 2007 (YouTube)]</ref> Other people with Usher syndrome have posted videos about their lives and condition on [[YouTube]], most notably Ginny Paja-Nyholm.<ref>[http://www.youtube.com/watch?v=e7yKsmO2qzI Ginny's trivia challenge for Usher syndrome]</ref> In October 2007, Candice, a mom living in Texas, began blogging about her two daughters, Jasmine and Rebecca; Rebecca has Usher syndrome I.<ref>{{cite web | author = Candice | url = http://ushersmom.blogspot.com/ | title = I'm adopting a Deaf child with Ushers, now what? | accessdate = 2007-11-07}}</ref>
Catherine Fischer has written a well-received autobiography of growing up with Usher syndrome in Louisiana, entitled ''Orchid of the Bayou''.<ref>{{cite book | author = Carroll C, Fischer CH | date = 2001 | title = Orchid of the Bayou: A Deaf Woman Faces Blindness | publisher = Gallaudet University Press | isbn = 978-1563681042}}</ref> Similarly, Vendon Wright has written two books describing his life with Usher syndrome, ''I was blind but now I can see''<ref>{{cite book | author = Wright V | date = 2007 | title = I was blind but now I can see | publisher = Authorhouse | isbn = 978-1420891010}}</ref> and ''Through my eyes''.<ref>{{cite book | author = Wright V | date = 2007 | title = Through my eyes | publisher = Pipers' Ash Ltd | isbn = 978-1904494867}}</ref> Louise Boardman has also written a short book called ''My son has Usher's Syndrome''.<ref>{{cite book | author = Boardman LS | date = 1985 | title = My son has Usher's Syndrome | publisher = Foundation Fighting Blindness | id = B0007207IG}}</ref>
Christian Markovic, an artist living with Usher syndrome, runs a company, Fuzzy Wuzzy Designs.<ref>[http://fuzzywuzzydesign.com/whosfuzzy.html Profile of Christian Markovic of Fuzzy Wuzzy Designs]</ref>
[[Spencer Tracy]]'s son John was a well-known person with Usher syndrome who lived a full life.<ref>[http://www.presstelegram.com/news/ci_6160671 Associated Press obituary for John Tracy]</ref> The [[John Tracy Clinic]] was founded in 1942 by his mother Louise to offer free help to parents of hearing-impaired infants and preschool children.<ref name="mets_2000" />
Jacob Desormeaux, son of horse-racing jockey [[Kent Desormeaux]], suffers from Usher syndrome. Jacob was born deaf and is progressively going blind. Kent dedicated his race in the [[Belmont Stakes]], which would give him and his horse [[Big Brown]] the Triple Crown, to his son Jacob. The family has started an organization to raise funds and awareness of the disease. Usher syndrome is disproportionately common among the [[Cajuns]] of south Louisiana, such as Desormeaux and Fischer, because of a genetic mutation among early French [[Acadian]] settlers in [[Nova Scotia]].
==References==
{{reflist|2}}
==Additional reading==
* {{cite book | author = Parker PM | date = 2007 | title = Usher Syndrome - A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers | publisher = ICON Group International | isbn = 978-0497113049}}
* {{cite book | author = Icon Health Publications | date = 2004 | title = The Official Patient's Sourcebook On Usher Syndrome: Directory For The Internet Age | edition = revised, updated edition | publisher = Icon Health Publications | isbn = 978-0597842030}}
* {{cite book | author = Stiefel SH, Lewis RA | date = 1991 | title = The Madness of Usher's: Coping With Vision and Hearing Loss/Usher Syndrome Type II | publisher = Business of Living Publications | isbn = 978-1879518063}}
* {{cite book | author = Duncan E, Prickett HT | date = 1988 | title = Usher's Syndrome: What It Is, How to Cope, and How to Help | publisher = Charles C. Thomas | isbn = 978-0398054816}}
* {{cite book | author = Vernon M | date = 1986 | title = Answers to your questions about Usher's syndrome (retinitis pigmentosa with hearing loss) | publisher = Foundation Fighting Blindness | id = ASIN B00071QLJ6}}
* {{cite book | author = Vernon M | date = 1969 | title = Usher's syndrome: Deafness and progressive blindness : clinical cases, prevention, theory and literature survey | publisher = Pergamon Press | id = ASIN B0007JHOJ4}}
== External links ==
===General information===
* [http://ghr.nlm.nih.gov/condition=ushersyndrome General overview from the NIH]
* [http://www.nidcd.nih.gov/health/hearing/usher.htm Usher Syndrome] Information from the National Institute on Deafness and Other Communication Disorders (NIDCD).
* [http://www.sense.org.uk/publications/allpubs/usher/U02.htm Information on Usher syndrome] from [http://www.sense.org.uk/ Sense], a British organization for deafblind people
* [http://www.genetests.org/servlet/access?id=8888890&key=JfyO7D5U2RFl-&gry=INSERTGRY&fcn=y&fw=PMan&filename=/glossary/profiles/usher1/details.html Scientific review of Usher 1]
* [http://www.genetests.org/servlet/access?id=8888890&key=c7bEsjGew9PEr&gry=INSERTGRY&fcn=y&fw=XLUO&filename=/glossary/profiles/usher2/details.html Scientific review of Usher 2]
===Resources===
* [http://www.nei.nih.gov/health/ushers/index.asp Usher Syndrome] Resource Guide from the National Eye Institute (NEI).
* [http://tr.wou.edu/CGI-BIN/WA.CGI?A0=USHERS Usher syndrome mailing list]
* [http://www.boystownhospital.org/UsherSyndrome/index.asp Boys Town National Research Hospital]
* [http://medicine.ucsd.edu/williams/index.html The Williams retinal Physiology Research Group, UCSD]
* http://www.dblink.org/lib/topics/usher-index.htm
* http://www.boystownhospital.org/Usher/information.asp
* http://www.boystownhospital.org/Usher/index.asp
* http://www.hearseehope.com
===Mutations===
* [http://www.retina-international.com/sci-news/ush1cmut.htm Mutations in USH1C]
[[Category:Genetic disorders]]
[[Category:Autosomal recessive disorders]]
[[Category:Otology]]
[[Category:Syndromes]]
[[de:Usher-Syndrom]]
[[fr:Syndrome d'Usher]]
[[he:תסמונת אשר]]
[[nl:Syndroom van Usher]]
[[no:Usher syndrom]]
[[pl:Zespół Ushera]]
[[pt:Síndrome de Usher]]
[[fi:Usherin oireyhtymä]]