J. Fielding Hejtmancik, M.D., Ph.D.
Ophthalmic Molecular Genetics Section
Building 5635FL, Room 1120
5635 Fishers Lane
Rockville, MD 20892-9402
One approach to understanding inherited visual diseases uses principles of positional cloning to identify genes important in human Mendelian inherited diseases. Such diseases currently undergoing linkage analysis, gene isolation, or characterization of mutations include retinitis pigmentosa, inherited cataracts, glaucoma, and a number of corneal dystrophies.
A second approach is to attempt to establish associations between DNA sequence changes in or near candidate genes and specific phenotypes. This type of study is most applicable to common diseases with a complex inheritance pattern, and is currently being used for age-related cataracts, primary open angle glaucoma, and high myopia.
Once a candidate gene has been identified and confirmed, the biochemical and pathophysiological implications of identified mutations are explored both in vitro through recombinant expression of native and mutant proteins, and in vivo through transgenic expression of pathological proteins. Many of these studies involve mutations in the lens crystallins, which make up more than 90 percent of the soluble protein of lens and are heavily modified in most cataracts. In addition, we have defined new developmental and physiological pathways as a result of our studies. Examples of this include the role of ZNF513 in retinal development and FYCO1 in lens development and transparency. We are pursuing these areas further using a combination of genetic, biochemical, and cell biological approaches. Finally, when possible, we apply our findings to improve the diagnostic and therapeutic approaches to the diseases we study.
Chen J, Ma Z, Jiao X, Fariss R, Kantorow WL, Kantorow M, Pras E, Frydman M, Pras E, Riazuddin S, Riazuddin SA, Hejtmancik JF. Mutations in FYCO1 cause autosomal-recessive congenital cataracts. Am J Hum Genet. 2011;88(6):827-838.
Li L, Nakaya N, Chavali VR, Ma Z, Jiao X, Sieving PA, Riazuddin S, Tomarev SI, Ayyagari R, Riazuddin SA, Hejtmancik JF. A mutation in ZNF513, a putative regulator of photoreceptor development, causes autosomal-recessive retinitis pigmentosa. Am J Hum Genet. 2010;87(3):400-9.
Li L, Jiao X, D'Atri I, Ono F, Nelson R, Chan CC, Nakaya N, Ma Z, Ma Y, Cai X, Zhang L, Lin S, Hameed A, Chioza BA, Hardy H, Arno G, Hull S, Khan MI, Fasham J, Harlalka GV, Michaelides M, Moore AT, Coban Akdemir ZH, Jhangiani S, Lupski JR, Cremers FPM, Qamar R, Salman A, Chilton J, Self J, Ayyagari R, Kabir F, Naeem MA, Ali M, Akram J, Sieving PA, Riazuddin S, Baple EL, Riazuddin SA, Crosby AH, Hejtmancik JF. Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa. PLoS Genet. 2018;14(8):e1007504.
Jiao X, Yang Z, Yang X, Chen Y, Tong Z, Zhao C, Zeng J, Chen H, Gibbs D, Sun X, Li B, Wakins WS, Meyer C, Wang X, Kasuga D, Bedell M, Pearson E, Weinreb RN, Leske MC, Hennis A, DeWan A, Nemesure B, Jorde LB, Hoh J, Hejtmancik JF, Zhang K. Common variants on chromosome 2 and risk of primary open-angle glaucoma in the Afro-Caribbean population of Barbados. Proc Natl Acad Sci U S A. 2009;106(40):17105-10.
Ma Z, Piszczek G, Wingfield PT, Sergeev YV, Hejtmancik JF. The G18V CRYGS mutation associated with human cataracts increases gammaS-crystallin sensitivity to thermal and chemical stress. Biochemistry. 2009;48(30):7334-41.
Related Scientific Focus Areas
Genetics and Genomics
Molecular Biology and Biochemistry
This page was last updated on August 17th, 2018