Usher syndrome (USH) is an autosomal recessive disorder characterized by progressive retinitis pigmentosa (RP) and moderate to profound sensorineural hearing loss. USH is the leading cause of combined deafness and blindness in the world and about 50% of all cases of combined deafness and blindness in the United States are due to Usher syndrome. The three major clinical subtypes (USH type I, USH type II and USH type III) are distinguished by severity of hearing loss and by the presence or absence of vestibular dysfunction. USH type I is genetically heterogeneous and the phenotype is the most severe of the three types of USH. Seven genetic loci have been mapped for USH1 and genes for five of them have been identified. At least three more genes for USH type I remain to be identified. In collaborations with scientists around the world, Dr. Friedman's lab has an unprecedented genetic resource to identify and study the genes involved in nonsyndromic as well as syndromic hearing impairment. From this resource, 1 have developed a unique collection of USH type I families with no mutations in the known USH genes and are either linked to USH1H locus or unlinked to known USH1 loci. As the Principal Investigator, my goal is to use these USH type I families forthe mapping and identification of new USH1 genes, including USH1H. My publication record on USH is indicative of my abilities to successfully conduct this research. My career goals are to understand the genetic and molecular basis of hearing processes through the identification and functional dissection of the genes involved in deafness. There are three specific aims of this proposal: 1) enrollment of additional families with an USHI phenotype and mutational screening of known USH loci, 2) linkage analyses to map the loci for USH1, and 3) positionally cloning of USHI H and additional USHI genes. Identification and characterization of these genes will enhance diagnostic accuracy and improve genetic counseling. Molecular dissection of USH will reveal important new information about the developmental, metabolic and/or regulatory pathways common to norma! retinal and auditory function.

Public Health Relevance

The knowledge gained from this study will improve our understanding of the biology and pathophysiology of the hearing and visual systems. A better understanding of the underlying causes of USH is a critical first step towards the development of effective therapies.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Transition Award (R00)
Project #
Application #
Study Section
Special Emphasis Panel (NSS)
Program Officer
Sklare, Dan
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Cincinnati Children's Hospital Medical Center
United States
Zip Code
Ali, R A; Rehman, A U; Khan, S N et al. (2012) DFNB86, a novel autosomal recessive non-syndromic deafness locus on chromosome 16p13.3. Clin Genet 81:498-500
Jaworek, Thomas J; Bhatti, Rashid; Latief, Noreen et al. (2012) USH1K, a novel locus for type I Usher syndrome, maps to chromosome 10p11.21-q21.1. J Hum Genet 57:633-7
Jaworek, Thomas J; Kausar, Tasleem; Bell, Shannon M et al. (2012) Molecular genetic studies and delineation of the oculocutaneous albinism phenotype in the Pakistani population. Orphanet J Rare Dis 7:44
Hufnagel, Robert B; Ahmed, Zubair M; Corrêa, Zélia M et al. (2012) Gene therapy for Leber congenital amaurosis: advances and future directions. Graefes Arch Clin Exp Ophthalmol 250:1117-28
Riazuddin, Saima; Ahmed, Zubair M; Hegde, Rashmi S et al. (2011) Variable expressivity of FGF3 mutations associated with deafness and LAMM syndrome. BMC Med Genet 12:21
Rehman, Atteeq U; Gul, Khitab; Morell, Robert J et al. (2011) Mutations of GIPC3 cause nonsyndromic hearing loss DFNB72 but not DFNB81 that also maps to chromosome 19p. Hum Genet 130:759-65
Friedman, Thomas B; Schultz, Julie M; Ahmed, Zubair M et al. (2011) Usher syndrome: hearing loss with vision loss. Adv Otorhinolaryngol 70:56-65
Hertzano, Ronna; Puligilla, Chandrakala; Chan, Siaw-Lin et al. (2010) CD44 is a marker for the outer pillar cells in the early postnatal mouse inner ear. J Assoc Res Otolaryngol 11:407-18
Riazuddin, S Amer; Shahzadi, Amber; Zeitz, Christina et al. (2010) A mutation in SLC24A1 implicated in autosomal-recessive congenital stationary night blindness. Am J Hum Genet 87:523-31