A major goal of my research has been to map genes that cause inherited diseasesaffecting the nervous system, the eye or the heart and to isolate these genes by positional cloning. We recently identified a defective gene which causes episodic ataxia and myokymia (EA-1). This autosomal dominant disorder causes episodes of dizziness and loss of coordination brought on by exertion or emotional stress. Attacks last from seconds to minutes, with normal function in between. The defective gene codes for a voltage-gated potassium channel; 7 different point mutations have been identified in 8 unrelated families with EA-1. Each mutation changes an amino acid residue that is invariant among the normal human, mouse, rat and fruit-fly genes. Studies in the Adelman lab to investigate the effect of these mutations on the electrophysiological properties of the channel have supported a dominant negative mechanism for the mutations. This was the first report of a naturally occurring potassium channel mutation in a vertebrate.

We have mapped and cloned 3 genes which cause autosomal dominant congenital cataracts (ADCC) in families. The genes in which these defects were found encode alpha-crystallin, beta crystallin and phakinin, a lens-specific intermediate filament protein.

Jakobs PM, Hanson EL, Crispell KA, Toy W, Keegan H, Schilling K, Icenogle TB, Litt M, Hershberger RE (2001). Novellamin A/C mutations in two families with dilated cardiomyopathy and conduction system disease. J Card Fail 7(3):249-56.

Jakobs P, Hess JP, FitzGerald PG, Kramer P, Weleber RG and Litt M (2000). Autosomal dominant congenital cataract associated with a deletion mutation in the human beaded filament protein gene BFSP2. Am J Hum Genet 66:1432-1436.

Litt M, Lamorticella DM, Bond CT, and Adelman J.P (1999). Gene structure and chromosomal mapping of the human small-conductance calcium activated potassium channel gene hSK1(KCNN1). Cytogenet Cell Genet 86:70-73.

Litt M, Kramer P, LaMorticella DM, Murphey W, Lovrien WE, and Weleber RG (1998). Autosomal dominant congenital cataract associated with a missense mutation in the human alpha crystallin geneCRYAA. Hum Mol Genet 7,471-474.

Litt M, Carrero-Valenzuela R, LaMorticella DM, Schultz DW, Mitchell TN, Krame P, and Maumenee IH (1997). Autosomal dominant cerulean cataract is associated with a chain termination mutation in the human beta crystallin gene CRYBB2. Hum Mol Genet 6,665-668.

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