Clinical diagnosis of the Usher syndromes

Smith, Richard J.H.; Berlín, Charles I.; Hejtmancik, J. F.; Keats, Bronya J.B.; Kimberling, William J.; Lewis, Richard A.; Möller, Claes; Pelias, Mary Z.; Tranebjærg, Lisbeth

doi:10.1002/ajmg.1320500107

Cited by 306 publications

(226 citation statements)

References 29 publications

(10 reference statements)

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“…The patients were diagnosed based on the diagnostic criteria for USH. 5 The group of patients was unselected. All USH patients with DNA available at the National Eye Clinic for the Visual Impaired at the Kennedy Center were included.…”

Section: Materials and Methods Patientsmentioning

confidence: 99%

“…Patients with USH1 have severe to profound congenital hearing impairment, prepubertal onset of RP and vestibular dysfunction. 5 In USH2 patients, the hearing loss is moderate to severe, the onset of RP is pre-or postpubertal, and the vestibular function is normal. Patients affected with USH3 have a moderate to severe progressive loss of hearing.…”

Section: Introductionmentioning

confidence: 99%

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Partial USH2A deletions contribute to Usher syndrome in Denmark

et al. 2015

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Usher syndrome is an autosomal recessive disorder characterized by congenital hearing impairment, progressive visual loss owing to retinitis pigmentosa and in some cases vestibular dysfunction. Usher syndrome is divided into three subtypes, USH1, USH2 and USH3. Twelve loci and eleven genes have so far been identified. Duplications and deletions in PCDH15 and USH2A that lead to USH1 and USH2, respectively, have previously been identified in patients from United Kingdom, Spain and Italy. In this study, we investigate the proportion of exon deletions and duplications in PCDH15 and USH2A in 20 USH1 and 30 USH2 patients from Denmark using multiplex ligation-dependent probe amplification (MLPA). Two heterozygous deletions were identified in USH2A, but no deletions or duplications were identified in PCDH15. Next-generation mate-pair sequencing was used to identify the exact breakpoints of the two deletions identified in USH2A. Our results suggest that USH2 is caused by USH2A exon deletions in a small fraction of the patients, whereas deletions or duplications in PCDH15 might be rare in Danish Usher patients.

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Section: Materials and Methods Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Partial USH2A deletions contribute to Usher syndrome in Denmark

et al. 2015

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“…1 Three clinical subtypes have been defined, with Usher syndrome type 1 (Usher 1) characterized by the most severe deafness at birth. 2 The blindness of Usher patients has characteristics of retinitis pigmentosa, although histological analyses of genetically-identified Usher retinas is currently lacking.…”

Section: Introductionmentioning

confidence: 99%

Lentiviral gene replacement therapy of retinas in a mouse model for Usher syndrome type 1B

Hashimoto¹,

et al. 2007

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One of the most disabling forms of retinal degeneration occurs in Usher syndrome, since it affects patients who already suffer from deafness. Mutations in the myosin VIIa gene (MYO7A) cause a major subtype of Usher syndrome, type 1B. Owing to the loss of function nature of Usher 1B and the relatively large size of MYO7A, we investigated a lentiviral-based gene replacement therapy in the retinas of MYO7A-null mice. Among the different promoters tested, a CMV-MYO7A chimeric promoter produced wild-type levels of MYO7A in cultured RPE cells and retinas in vivo. Efficacy of the lentiviral therapy was tested by using cell-based assays to analyze the correction of previously defined, MYO7A-null phenotypes in the mouse retina. In vitro, defects in phagosome digestion and melanosome motility were rescued in primary cultures of RPE cells. In vivo, the normal apical location of melanosomes in RPE cells was restored, and the abnormal accumulation of opsin in the photoreceptor connecting cilium was corrected. These results demonstrate that a lentiviral vector can accommodate a large cDNA, such as MYO7A, and mediate correction of important cellular functions in the retina, a major site affected in the Usher syndrome. Therefore, a lentiviral-mediated gene replacement strategy for Usher 1B therapy in the retina appears feasible.

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“…CDH23 is mutated in Usher's syndrome type 1D (USH1D) and MYO7A in USH1B patients (Weil et al 1995;Bolz et al 2001;Bork et al 2001). Patients with USH1 are congenitally deaf, have vestibular dysfunction, and develop retinitis pigmentosa (Smith et al 1994). Both genes have also been shown to underlie nonsyndromic forms of deafness (Liu et al 1997a,b;Weil et al 1997;Bork et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Progressive Hearing Loss and Increased Susceptibility to Noise-Induced Hearing Loss in Mice Carrying a Cdh23 but not a Myo7a Mutation

Holme

Steel

2004

JARO - Journal of the Association for Research in Otolaryngolog

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Exposure to intense noise can damage the stereocilia of sensory hair cells in the inner ear. Since stereocilia play a vital role in the transduction of sound from a mechanical stimulus into an electrical one, this pathology is thought to contribute to noise-induced hearing loss. Mice homozygous for null mutations in either the myosin VIIa (Myo7a) or cadherin 23 (Cdh23) genes are deaf and have disorganized stereocilia bundles. We show that mice heterozygous for a presumed null allele of Cdh23 (Cdh23 v ) have low-and high-frequency hearing loss at 5-6 weeks of age, the high-frequency component of which worsens with increasing age. We also show that noise-induced hearing loss in 11-12-week-old Cdh23 v heterozygotes is two times greater than for wild-type littermates. Interestingly, these effects are dependent upon the genetic background on which the Cdh23 v mutation is carried. Noise-induced hearing loss in 11-12-week-old mice heterozygous for a null allele of Myo7a (Myo7a 4626SB ) is not significantly different from wildtype littermates. CDH23 is the first gene known to cause deafness in the human population to be linked with predisposition to noise-induced hearing loss.

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Clinical diagnosis of the Usher syndromes

Cited by 306 publications

References 29 publications

Partial USH2A deletions contribute to Usher syndrome in Denmark

Partial USH2A deletions contribute to Usher syndrome in Denmark

Lentiviral gene replacement therapy of retinas in a mouse model for Usher syndrome type 1B

Progressive Hearing Loss and Increased Susceptibility to Noise-Induced Hearing Loss in Mice Carrying a Cdh23 but not a Myo7a Mutation

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