Much of the hospital's success in identifying and treating children with hearing loss is the result of the rapid transfer of research findings from laboratories to clinic and bedside.

Areas of Research - Hereditary Communication Disorders - Gene Markers

Research in this laboratory, under the direction of Dr. William J. Kimberling, is concerned with identification of genes and the localization of these genes to the human gene map. Syndromes currently under study include:

Usher
Branchio-oto-renal
Autosomal dominant progressive hearing loss
Nonsydromic recessive hearing loss
Cleft palate

A major focus of the research program has been on Usher syndrome. Eleven different Usher genes have been discovered; one has been identified as the myosin VIIa gene on chromosome 11q, and a second is a novel basement membrane protein called Usherin. Our laboratory is now attempting to isolate and clone other Usher genes. The series of Usher families under study is the largest ever assembled.

Future research will be centered on the causes of variation in the expression of the Usher genes, on the development of animal models (with Dr. Cosgrove) and on methods of gene therapy. Another project (with Dr. Kelley) is the gene mapping of genes causing progressive hearing loss.

One gene on chromosome 1p has already been identified and others are currently being investigated. Branchio-oto-renal syndrome is another major project of the laboratory. One gene has been located on chromosome 8, and this gene has recently been cloned. Nonsyndromic recessive hearing loss is another major study focus. NSRHL accounts for 80 percent of all hereditary cases. It has been estimated that 15 to 300 genes may be involved. Our work is now directed towards finding these genes.

Facilities

The laboratory is equipped for most techniques in gene marker analysis including typing of DNA polymorphisms. It has the power supplies and electrophoretic equipment required for starch, acrylamide, and agarose electrophoresis isoelectric focusing. It also has a darkroom, ultracentrifuge, ultra-low temperature freezers, sterile hood incubators and autoclave.

Representative Publications

Kimberling, W.J. & Möller, C.G. (1995). Clinical and molecular

genetics of Usher Syndrome. J. Am. Acad. Audiol. 6, 63-72.

Steel, K.P. & Kimberling, W.J. (1996). Approaches to understanding

the molecular genetics of hearing and deafness. In T.R. Van de

Water, A.N. Popper & R. Fay (Eds.), Clinical Aspects of Hearing

(Springer Handbook of Auditory Research) . Springer, NY,

pp. 10-40.

Weston, M.D., Kelley, P.M., Overbeck, L.D., Hasson, T., Orten, D.,

Chen, Z.Y., Corey, D., Moosekers, M.S., Sumegi, J., Cremers, C.,

Möller, C., Jacobsen, S. & Kimberling, W.J. (1996). Myosin VIIa

mutation screening in 189 Usher syndrome type 1 patients. Am. J.

Hum. Genet. 59 , 1074-1083.

Cohn, E.S., Kelley, P.M., Fowler, T., Gorga, M.P., Lefkowitz, D., Kuehn,

H., Schaefer, G.B., Gobar, L.S., Hahn, F.J., Harris, D.J. &

Kimberling, W.J. (1999). Clinical studies of families with hearing

loss attributable to mutations in the connexin 26 gene

(GJB 2 /DFNB 1 ). Pediatrics 103, 546-550.

Pieke-Dahl, S., Möller, C.G., Kelley, P.M., Astuto, L.M., Cremers,

C.W.R.J., Gorin, M.B. & Kimberling, W.J. (2000). Genetic

heterogeneity of Usher syndrome type II: Localization to

chromosome 5 q. Am. J. Med. Genet. 37, 256-262.

Weston, M.D., Eudy, J.D., Fujita, S., Yao, S.-F., Sumegi, J. &

Kimberling, W.J. (2000). Genomic structure of the Usher

syndrome type 2 A (USH 2 A) gene. Genomics 66, 1199-1210.

Eudy, J.D., Talmadge, C.B., Weston, M.D., Yao, S-F, Dooley, C.M.,

Bhattacharaya, G., Cosgrove, D., Ahmad, I., Kimberling, W.J. &

Sumegi, J. (submitted). The protein product of the murine

orthologue of Usher Syndrome type IIa gene localizes to the

interphotoreceptor cell matrix. Hum. Mol. Genet.