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NEUROLOGY 1991;41:992
© 1991 American Academy of Neurology

Predictive testing for Wilson's disease using tightly linked and flanking DNA markers

L. A. Farrer, PhD, A. M. Bowcock, PhD, J. M. Hebert, MA, B. Bonné-Tamir, PhD, I. Sternlieb, MD, M. Giagheddu, MD, P. St. George-Hyslop, MD, M. Frydman, MD, J. Lössner, DrScMed, L. Demelia, MD, C. Carcassi, MD, R. Lee, BA, R. Beker, MS, A. E. Bale, MD, H. Donis-Keller, PhD, I. H. Scheinberg, MD and L. L. Cavalli-Sforza, MD

Department of Neurology (Dr. Farrer and R. Lee) and the School of Public Health (Dr. Farrer), Boston University School of Medicine, Boston, MA; the Department of Neurology (Dr. Farrer), Harvard Medical School, Boston, MA; Department of Genetics (Drs. Bowcock, Hebert, and Cavalli-Sforza), Stanford University School of Medicine, Stanford, CA; the Department of Human Genetics (Drs. Bonné-Tamir and Frydman, and R. Beker), Sackler School of Medicine, Tel Aviv University, Israel; Albert Einstein College of Medicine (Drs. Sternlieb and Scheinberg), New York, NY; Istituti di Clinica Neurologica e Medica (Drs. Giagheddu, Demelia, and Carcassi), Università di Cagliari, Italy; the Departments of Neurology and Medicine (Dr. St. George-Hyslop), University of Toronto, Toronto, Canada; Pediatric Genetics Clinic (Dr. Frydman), Hasharon Hospital, Petah Tiqwa, Israel; the Department of Neurology (Dr. Lössner), Karl Marx University, Leipzig, East Germany; the Department of Human Genetics (Dr. Bale), Yale University School of Medicine, New Haven, CT; and the Department of Genetics (Dr. Donis-Keller), Washington University, St. Louis, MO.

We studied DNA polymorphisms for five new chromosome 13 markers in 52 Wilson's disease (WD) families from Europe, North America, and the Middle East. There was significant evidence for linkage between the Wilson's disease locus (WND) and all the marker loci. Multilocus linkage analysis, using a genetic linkage map established from reference pedigrees, suggested that WND is most likely between D13S31 and D13S59, at distances of 0.4 and 1.2 centimorgans, respectively. Our results suggest that the chromosomal location of the Wilson's disease gene is the same in all families from the populations studied. This evidence and the availability of many close, flanking, and polymorphic DNA markers make possible accurate and informative testing of potential carriers and WD homozygotes in families with at least one previously affected child. An advantage of a genetic linkage test over other laboratory methods for prediction of genotype in WD is that a reliable diagnosis can be made at a much earlier stage in life, including prenatally. In addition, DNA testing can be used in place of an invasive liver biopsy procedure to confirm a diagnosis in patients with borderline serum ceruloplasmin levels. Presymptomatic identification will also allow therapeutic intervention to prevent symptoms before irreparable liver or neurologic damage occurs. We describe the implementation of prenatal and preclinical diagnosis for two families with WD.

Address correspondence and reprint requests to Dr. Lindsay Farrer, Boston University School of Medicine, Department of Neurology, 80 East Concord Street Boston, MA 02118.

Supported by National Institutes of Health grants NS26454, GM28428, and DK34668; U.S.-Israel Binational Science Foundation grant 85-00337; and the National Center for the Study of Wilson's Disease.

Received October 31, 1990. Accepted for publication in final form December 13, 1990.




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Hum. Mol. Genet., August 12, 2000; 9(13): 1927 - 1935.
[Abstract] [Full Text] [PDF]


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