Three clinical types of Usher Syndromes have been described that are distinguished largely by a characterization of the patient’s history of hearing loss, balance difficulties, and the development of night blindness due to retinitis pigmentosa. Types I, II, and III are themselves clinically variable. Differences are exhibited in the extent and age of onset of the hearing loss and balance dysfunction. Particularly significant is the variability observed regarding the appearance of vision loss and night blindness due to retinitis pigmentosa (RP). The observed RP varies with the age of onset, the pattern of retinal deposition of spicule-shaped pigment deposits, the rate of progress of vision loss, and the visual capability of the affected individual in the late stages of the disease.
Ten well-characterized genes, USH genes, have been identified to cause the Usher syndromes. Many mutant alleles of these genes have been identified in people from around the world. Additional USH genes may be identified as more affected individuals are studied and genetic analysis techniques improve. Some of the observed phenotypic variability can be accounted for by the genetic complexity underlying the Usher syndromes. All of the Usher syndrome mutations identified to date are autosomal recessive mutations. This means that the affected individual carries two mutant versions (or alleles) of a particular USH gene, one inherited from the father and the other from the mother. The parents will be unaffected if they carry one functional allele and one mutant allele of the gene.
Dr. Michels initiated this project with colleagues from New York Medical College: Dr. Marc Epstein, OD, a low vision specialist and Dr. Cono Grasso, MD, chairman of the Ophthalmology Department - Queens and Jamaica Hospital. Dr. Epstein consults at the Helen Keller National Center for the Deaf – Blind Adults and Youth (HKNC), located in Sands Point NY, a training and education center for the deaf – blind. Approximately 50% of the HKNC trainees have Usher syndrome and we will be recruiting participants for our study from these individuals. We joined with a team of researchers in the National Eye Institute and National Institute of Deafness and Communication Disorders of the National Institutes of Health, who are carrying out a clinical study of Usher syndrome. The Principal Investigator of the clinical study is Dr. Wadih Zein, MD and Drs. Epstein, Grasso, and Michels have been appointed Associate Investigators of the Usher syndrome clinical study.
This clinical study has as its primary objectives to enhance understanding of the natural history of the Usher Syndromes, that is, to thoroughly characterize the clinical phenotype of affected individuals and follow the progress of any clinical changes over a 5 year period, and to determine whether there is a correlation between genotype and the phenotype in Usher syndrome affected individuals. An important question that this clinical study hopes to answer is to what extent does the phenotype vary among affected individuals carrying the identical mutant alleles? This type of information is an essential “control” for any investigations of new treatment protocols. One must know the range of normal variation in phenotype in order to judge whether or not an experimental treatment is slowing the progress of the disease.
Another important goal of the project is to identify new genes that cause Usher syndrome. The underlying cell biology of the known USH gene products suggests that far more than 10 proteins are likely involved. Most recently, novel alleles of DFBN genes (for non-syndromic deafness - deafness without blindness) were shown to cause Usher. Thus, identifying more Usher mutations will enable us to identify more pleiotropic gene functions involved in development of vision, hearing, and balance organs.
The Usher syndrome project is currently not registering new subjects. Manuscripts are in preparation. We look forward to continuing our participation in this clinical study.
Ten well-characterized genes, USH genes, have been identified to cause the Usher syndromes. Many mutant alleles of these genes have been identified in people from around the world. Additional USH genes may be identified as more affected individuals are studied and genetic analysis techniques improve. Some of the observed phenotypic variability can be accounted for by the genetic complexity underlying the Usher syndromes. All of the Usher syndrome mutations identified to date are autosomal recessive mutations. This means that the affected individual carries two mutant versions (or alleles) of a particular USH gene, one inherited from the father and the other from the mother. The parents will be unaffected if they carry one functional allele and one mutant allele of the gene.
Dr. Michels initiated this project with colleagues from New York Medical College: Dr. Marc Epstein, OD, a low vision specialist and Dr. Cono Grasso, MD, chairman of the Ophthalmology Department - Queens and Jamaica Hospital. Dr. Epstein consults at the Helen Keller National Center for the Deaf – Blind Adults and Youth (HKNC), located in Sands Point NY, a training and education center for the deaf – blind. Approximately 50% of the HKNC trainees have Usher syndrome and we will be recruiting participants for our study from these individuals. We joined with a team of researchers in the National Eye Institute and National Institute of Deafness and Communication Disorders of the National Institutes of Health, who are carrying out a clinical study of Usher syndrome. The Principal Investigator of the clinical study is Dr. Wadih Zein, MD and Drs. Epstein, Grasso, and Michels have been appointed Associate Investigators of the Usher syndrome clinical study.
This clinical study has as its primary objectives to enhance understanding of the natural history of the Usher Syndromes, that is, to thoroughly characterize the clinical phenotype of affected individuals and follow the progress of any clinical changes over a 5 year period, and to determine whether there is a correlation between genotype and the phenotype in Usher syndrome affected individuals. An important question that this clinical study hopes to answer is to what extent does the phenotype vary among affected individuals carrying the identical mutant alleles? This type of information is an essential “control” for any investigations of new treatment protocols. One must know the range of normal variation in phenotype in order to judge whether or not an experimental treatment is slowing the progress of the disease.
Another important goal of the project is to identify new genes that cause Usher syndrome. The underlying cell biology of the known USH gene products suggests that far more than 10 proteins are likely involved. Most recently, novel alleles of DFBN genes (for non-syndromic deafness - deafness without blindness) were shown to cause Usher. Thus, identifying more Usher mutations will enable us to identify more pleiotropic gene functions involved in development of vision, hearing, and balance organs.
The Usher syndrome project is currently not registering new subjects. Manuscripts are in preparation. We look forward to continuing our participation in this clinical study.