The Basic Biology of Aging at the University of Washington
Karen G. Stephens, Ph.D.

Email: millie@u.washington.edu

Dr. Stephens is concerned with mapping and investigating the mechanism of germline contiguous gene deletions spanning neurofibromatosis type 1 (NF1), screening for somatic NF1 microdeletions in mosaic patients, and identifying genes in microdeletion that may account for the early onset of dermal neurofibromas associated with the microdeletion. To determine the molecular basis of NF1 microdeletion mediated by flanking 60kb repeats (NF1REP), her laboratory is trying to determine if NF1REP polymorphism predisposes certain individuals to NF1 microdeletion and whether NF1 microdeletion increases the risk of developing a solid tumor malignancy.

They are exploring the feasibility of using real time quantitative PCR to identify and fine map allelic gains and losses in malignant peripheral nerve sheath tumors. They also support the Interdisciplinary Basic Research in Dermatology program by providing clinical diagnosis and collection of tissue samples, constructing immortalized cell lines, DNA sequencing, genetic linkage analyses, and the application of other molecular genetic techniques.

Dr. Stephens is Research Associate Professor, Department of Laboratory Medicine and Department of Medicine, Division of Medical Genetics; Adjunct Research Associate Professor and Member, Graduate Faculty, Department of Pathology; and Co-Director, Genetics Section, Molecular Diagnosis Laboratory, Department of Laboratory Medicine.

Selected Relevant Publications
Leppig KA, Kaplan P, Viskochil D, Weaver M, Ortenberg J, Stephens K. Familial NF1 contiguous gene deletions: cosegregation with distinctive facial features and early onset of cutaneous neurofibromas. Am J Med Genet 73:197-204, 1997.

Sybert VP, Frances JS, Corden LD, Smith LT, Weaver M, Stephens K, McLean WHI. Cyclic ichthyosis with epidermolytic hyperkeratosis: a phenotype conferred by mutations in the 2B domain of keratin 1. Am J Hum Genet 64:732-738, 1999.

Dorschner MO, Sybert VP, Weaver M, Pletcher B, Stephens K. NF1 microdeletion breakpoints are clustered at flanking repetitive sequences. Hum Mol Genet 9:35-46, 2000.

Potter NT, Nance MA, and the Ataxia Molecular Diagnostic Testing Group: Allingham-Hawkins DJ, Bellissimo D, Bridge P, Graham L, Brown C, Garber A, Leonard D, Rennert H, Margolis R, McIntosh N, Muralidharan K, Popovich B, Anoe K, Ray P, Richards CS, Gunaratne P, Schaefer F, Seltzer W, Sims K, Xin W, Snow K, Stephens K, Wick M. Genetic Testing for Ataxia in North America. Mol Diagn 5:91-99, 2000.

Stephens K, Tait JF, Jacobs DS,Garg U. Molecular Genetic Testing. In: Jacobs and DeMott Laboratory Test Handbook, 5th ed. DS Jacobs, WR DeMott, DK Oxley, eds. Lexi-Comp Inc, Cleveland, 2001. pp 701-718.

Livingston RJ, Sybert VP, Smith LT, Dale BA, Presland RB, Stephens K. Expression of a truncated keratin 5 may contribute to severe palmar/plantar hyperkeratosis in EB simplex patients. J Invest Dermatol 116:970-974, 2001.

López-Correa C, Dorschner MO, Brems H, Lázaro C, Clementi M, Upadhayaya M, Dooijes D, Moog U, Kehrer-Sawatzki H, Rutkowski JL, Fryns J-P, Marynen P, Stephens K, Legius E. Recombination hotspot in NF1 microdeletion patients. Hum Mol Genet 10:1387-1392, 2001.

Dorschner MO, Barden D, Stephens K. Diagnosis of five spinocerebellar ataxia disorders by multiplex amplification and capillary electrophoresis. J Mol Diagn, in press.