Characterization of Usher Syndrome Type 1 Heterogeneity by Genetic and Phenotypic Analyses
No Thumbnail Available
Authors
Astuto, Lisa Marie
Issue Date
2002
Type
Dissertation
Language
en_US
Keywords
Alternative Title
Abstract
Patients with Usher syndrome type I suffer from sensorineural hearing impairment, retinal degeneration and often, vestibular dysfunction. Significant genetic heterogeneity exists as seven different genes are currently believed to cause Usher syndrome type 1. Three of the four identified genes encode the myosin Vila, cadherin 23 and protocadherin 15 proteins. A nonsyndromic deafness association has been reported with each of these genes demonstrating additional clinical heterogeneity.|This research was undertaken to prove or disprove the following hypotheses: 1) not all the Usher I subtypes exist and 2) MYO7A does not cause a significant fraction of nonsyndromic recessive hearing loss and any RNSHL proband carrying a pathologic mutation in an USH1 gene will present undetected retinitis pigmentosa confirming a missed diagnosis of Usher syndrome. This work was conducted on a large sample of Usher type I and recessive nonsyndromic deafness families negative for mutations in MYO7A and GJB2, respectively. Results of linkage and heterogeneity analyses of the Usher families revealed important epidemiological data presenting no evidence for the USH1A and USH1E subtypes and demonstrating the second most common type of Usher I is due to one or more genes on chromosome 10. Mutation and clinical analyses of both the Usher and RNSHL persons with mutations in CDH23 and PCDH15 present a wide range of hearing loss and RP phenotypes, differing in severity, age of onset, type and the presence or absence of vestibular areflexia. Continued molecular and clinical evaluation of these genes, as well as the remaining Usher genes, is necessary for further characterization that will ultimately lead to increased availability of accurate diagnostic and presymptomatic genetic testing options, early intervention, and disease based treatments.
Description
Citation
Publisher
Creighton University
License
Copyright is retained by the Author.
A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.