Allelic hierarchy of CDH23 mutations causing non-syndromic deafness DFNB12 or Usher syndrome USH1D in compound heterozygotes

Recessive mutations that disable cadherin 23, a protein encoded by CDH23, cause type 1 Usher syndrome (USH1D), which is characterized by deafness, vestibular dysfunction and vision loss due to retinitis pigmentosa. However, some milder mutations of CDH23 cause deafness alone (DFNB12). The clinical presentation in individuals that have one DFNB12 mutation in combination with one USH1D mutation is not known and cannot be predicted from current data. We identified five individuals that have a combination of CDH23 mutations where one of the two recessive mutations is a known or predicted USH1 mutation. These five individuals are deaf and have normal vision and balance. These data indicate that one DFNB12 mutation of CDH23 can maintain vision and balance in the presence of an USH1D mutation. This finding has important implications for genetic counseling of individuals with CDH23 mutations. These data also raise hope for the development of a therapy for vision loss in Usher syndrome patients, as it appears that even some amount of imperfect cadherin 23 protein in the retina can prevent the loss of vision. (By Julie M. Schultz, Ph.D., )

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