An Evaluation of Genetic Carriers of Usher's Syndrome

Holland, Monte G.; Cambie, E.; Kloepfer, Warner

doi:10.1016/0002-9394(72)91215-9

Cited by 16 publications

(6 citation statements)

References 11 publications

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“…Even 'minor degrees of impairment' in 3 additional carriers noted by the same authors were not seen in the present study. In addition, fundus changes showing phenotypic similarities to those noted in gyrate atrophy of the choroid and retina, as reported by Holland et al (1972) in 2 definite and 1 possible heterozygous carriers, were not seen in our 14 subjects.…”

Section: Discussioncontrasting

confidence: 49%

“…Since they did not indicate either the specific manner in which thresholds were measured on the other 2 subjects with minimal degrees of elevation (for example, size of the test target, locus of the retina being tested) or their range of normal values, it was difficult to interpret the significance of a 0 5 log unit elevation. Holland et al (1972) reported gyrate-atrophy-like changes in 2 sisters (ages 80 and 75 years), one of whom was a definite heterozygote for Usher's Stuart Sondheimer, Gerald A. Fishman, Rockefeller S. Young, and Victoria A. Vasquiez syndrome while the other had a 50% probability of carrying the gene for this disease. Both sisters were aphakic and highly myopic.…”

Section: Discussionmentioning

confidence: 99%

“…In some carriers the increase is associated with fundus changes characteristic of gyrate atrophy of the choroid and retina (Holland et al, 1972). Because of the importance of identifying heterozygotes, we examined 14 Usher's syndrome carriers to confirm the presence of either dark adaptation abnormalities or fundus abnormalities, particularly those suggestive of gyrate atrophy of the choroid and retina.…”

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confidence: 99%

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Dark adaptation testing in heterozygotes of Usher's syndrome.

Sondheimer¹,

Fishman²,

Young³

et al. 1979

British Journal of Ophthalmology

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Section: Discussioncontrasting

confidence: 49%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Dark adaptation testing in heterozygotes of Usher's syndrome.

Sondheimer¹,

Fishman²,

Young³

et al. 1979

British Journal of Ophthalmology

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“…No abnormalities in the dark adaptation kinetics have been recently found in USH1B patients [20]. However, delayed recovery of rod sensitivity after light desensitization has been reported in carrier and affected USH patients [51], [52] as well as in individuals with retinitis pigmentosa [53], [54], [55]. In any case the recovery from light desensitization represents an important functional read-out to test the efficacy of experimental therapies for the USH1B retina at the pre-clinical level.…”

Section: Discussionmentioning

confidence: 99%

Myosin7a Deficiency Results in Reduced Retinal Activity Which Is Improved by Gene Therapy

et al. 2013

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Mutations in MYO7A cause autosomal recessive Usher syndrome type IB (USH1B), one of the most frequent conditions that combine severe congenital hearing impairment and retinitis pigmentosa. A promising therapeutic strategy for retinitis pigmentosa is gene therapy, however its pre-clinical development is limited by the mild retinal phenotype of the shaker1 (sh1−/−) murine model of USH1B which lacks both retinal functional abnormalities and degeneration. Here we report a significant, early-onset delay of sh1−/− photoreceptor ability to recover from light desensitization as well as a progressive reduction of both b-wave electroretinogram amplitude and light sensitivity, in the absence of significant loss of photoreceptors up to 12 months of age. We additionally show that subretinal delivery to the sh1−/− retina of AAV vectors encoding the large MYO7A protein results in significant improvement of sh1−/− photoreceptor and retinal pigment epithelium ultrastructural anomalies which is associated with improvement of recovery from light desensitization. These findings provide new tools to evaluate the efficacy of experimental therapies for USH1B. In addition, although AAV vectors expressing large genes might have limited clinical applications due to their genome heterogeneity, our data show that AAV-mediated MYO7A gene transfer to the sh1−/− retina is effective.

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“…De Haas et al [1970] noticed that the incidence of abnor mal EOG in his series was too high and too constant to be accounted for by normal variability. In other studies, abnormal EOGs wei'e also found in a high proportion of carriers [Holland et al, 1972;Davenport et a l, 1978;Pinckers et al, 1994;Van Aarem et al, 1995], The mean EOG light peak/dark trough ratio in carriers of Usher syndrome type I was significantly lower com pared to that in normal controls. In carriers of Usher syndrome type II, the difference in this ratio was even more significant (P < 0,0005) compared to normal con trols [Pinckers et al, 1994].…”

Section: Discussionmentioning

confidence: 67%

Clinical findings in obligate carriers of type I Usher syndrome

et al. 1995

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Seventeen obligate carriers from nine families with autosomal recessive Usher syndrome type I underwent otological, audiological, vestibular, and ophthalmological examination in order to identify possible manifestations of heterozygosity. Linkage studies were performed and six families showed linkage to chromosome region 11q13.5 while 3 families have so far failed to show linkage to the candidate regions. Eight obligate carriers had an abnormal puretone audiogram. Two different audiometric patterns could be distinguished when hearing loss was corrected for age and sex. Four carriers (24%) had significant sensorineural hearing loss (SNHL) which increased at higher frequencies. The other 13 carriers had SNHL of about 10 dB at 0.25 and 0.5 kHz, but less at higher frequencies. Vestibular findings were generally normal. Electrooculography demonstrated a significant lower mean light peak/dark trough ratio in Usher type I carriers compared to normal control individuals. The methods used in this study were found not to be specific enough to clinically identify carriers of Usher type I syndrome. Nevertheless it is remarkable that a number of obligate carriers showed significant audiological and ophthalmological abnormalities. © 1995 Wiley‐Liss, Inc.

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An Evaluation of Genetic Carriers of Usher's Syndrome

Cited by 16 publications

References 11 publications

Dark adaptation testing in heterozygotes of Usher's syndrome.

Dark adaptation testing in heterozygotes of Usher's syndrome.

Myosin7a Deficiency Results in Reduced Retinal Activity Which Is Improved by Gene Therapy

Clinical findings in obligate carriers of type I Usher syndrome

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