Gerstmann-Straussler-Scheinker disease with mutation at codon 102 and methionine at codon 129 of PRNP in previously unreported patients

Jones, C.K. BS
Piccardo, P. MD
Lazzarini, A. MS
Golbe, L.I. MD
Zimmerman, T.R. Jr. MD
Dickson, D.W. MD
McLachlan, D.C. MD
St. George-Hyslop, P. MD
Lennox, A. MPH
Perlman, S. MD
Vinters, H.V. MD
Hodes, M.E. MD PhD
Dlouhy, S. PhD
Ghetti, B. MD

From the Department of Medical and Molecular Genetics (Drs. Young, Hodes, Dlouhy, and Ghetti), the Graduate Program in Medical Neurobiology (Dr. Ghetti and C. Jones), and the Department of Pathology and Laboratory Medicine (Drs. Piccardo and Ghetti), Indiana University School of Medicine, Indianapolis, IN; the Department of Neurology (Drs. Golbe and Zimmerman, and A. Lazzarini), UMDNJ Robert Wood Johnson Medical School, New Brunswick, NJ; the Department of Pathology (Dr. Dickson), Albert Einstein College of Medicine, Bronx, NY; the Division of Neurology and Center for Research in Neurodegenerative Disease (Drs. McLachlan and St. George-Hyslop), University of Toronto, ON, Canada; the Geriatric Psychiatry Service and FAD Registry (A. Lennox), Queen Elizabeth Hospital, Toronto, ON, Canada; and the Departments of Neurology (S. Perlman) and Pathology and Laboratory Medicine (Dr. Vinters), and the Brain Research Institute (Dr. Vinters), UCLA Medical Center, Los Angeles, CA.
Supported in part by PHS grants NS29822 and P30 AG10133 (B.G.) and AG10123 (H.V.V.).
Received August 1, 1994. Accepted in final form November 2, 1994.
Address correspondence and reprint requests to Dr. B. Ghetti, Department of Pathology and Laboratory Medicine, Indiana University Medical Center, Medical Science Building Rm A138, Indianapolis, IN 46202.

Neurology 45(6):p 1127-1134, June 1995.

We present two patients with Gerstmann-Staussler-Scheinker disease (GSS), one from a previously undescribed kindred and one from the Canadian branch of a previously reported British kindred. In both patients, GSS is caused by a substitution of thymine for cytosine at codon 102 of the prion protein gene (PRNP). In each patient, we confirmed the clinical diagnosis by neuropathologic examination. The mutation, causing a substitution of leucine for proline at residue 102 (P102L) of the prion protein, has been previously reported in at least 30 other families. In the patients described here, the mutation was in coupling with methionine at PRNP codon 129.

NEUROLOGY 1995;45

1127-1134