Throughout her career, Corinne Michels, a distinguished professor of biology at CUNY’s Queens College, has sought to understand the genetic mechanisms that underlie the functions of living systems. The National Institutes of Health recently named her an associate investigator in a major clinical study of Usher syndromes, a group of inherited disorders that cause deafness and blindness. Here is her description of her research:
In the last year, I have been developing a new area of research – a natural history and genetic study of the Usher syndromes. The Usher syndromes are a group of inherited deaf-blindness disorders sometimes associated with balance problems.
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 [or RP, a degeneration of retinal cells].
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 RP. The observed RP varies with the age of onset, the pattern of retinal deposition of spicule- [needle-] 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.
Nine well-characterized genes, USH genes, plus two others that are less well characterized, are known to cause the Usher syndromes. Moreover, many mutant alleles [forms] 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 [“autosomal” refers to non-sex chromosomes]. 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.
I am … approved as an Associate Investigator on an NIH Clinical Study entitled, “Natural History and Genetic Studies of Usher Syndrome” funded by the National Eye Institute. I will be working with colleagues from New York Medical College, an ophthalmologist and a low vision specialist, and the work will be done at the Helen Keller National Center for the Deaf- Blind … a training and education center for the deaf-blind.
Approximately 30% of the HKNC trainees have an Usher syndrome and we will be recruiting participants for our study from these individuals. This clinical study has as its primary objectives to enhance our understanding of the natural history of the Usher Syndromes, that is, to thoroughly characterize the clinical phenotype [appearance reflecting genes and environment] 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 [genetic makeup] 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.
