Nature Genetics
13, 114 - 116 (1996)
doi:10.1038/ng0596-114
Localization of the gene for Cowden disease to chromosome 10q22−23M.R. Nelen1, G.W. Padberg1, 16, E.A.J. Peeters2, A.Y. Lin3, B. van den Helm4, R.R. Frants5, V. Goulon6, A.M. Goldstein3, M.M.M van Reen4, D.F. Eastern7, R.A. Eeles8, S. Hodgson9, J.J. Mulvihill10, V.A. Murday11, M.A. Tucker12, E.C.M. Mariman4, T.M. Starink13, B.A.J. Ponder14, H.H. Ropers4, H. Kremer4, M. Longy6
& C. Eng14, 15, 16
1Dept of Neurology, Univ Hosp Nijmegen, P.O Box 9101,6500HB, Nijmegen, The Netherlands
2Dept of Neurology, Leiden Univ, The Netherlands
3National Cancer Inst, National Insts of Health, Rockville, Maryland, USA
4Dept of Human Genetics, Univ Hosp Nijmegen, The Netherlands
5MGC-Dept of Human Genetics, Leiden Univ, The Netherlands
6Oncologie Moleculaire, Institut Bergonie, Bordeaux, France
7CRC Genetic Epidemiology Research Group, Inst of Public Health, Cambridge, UK
8Inst of Cancer Research, Royal Marsden Hosp, Sutton, Surrey, UK
9Clinical Genetics Dept, Guys and St. Thomas Hosps, London, UK
10Dept. Of Human Genetics, Univ of Pittsburg,Pittsburg, PA, USA
11Clinical Genetics Dept, St.George's Hosp, London, UK
12Genetic Epidemiology Branch, National Cancer Intitute, Rockville, MD, USA
13Dept of Dermatology, Free Univ Hosp Amsterdam, The Netherlands
14CRC Human Cancer Genetics Research Group, Univ of Cambridge, UK
15Division of Cancer Epidemiology and Control, Dana-Farber Cancer Inst, Dept of Medicine, Harvard Med School D920C, 44 Binney Street, Boston, Massachusetts 02115-6084, USA
16, Correspondence should be addressed to G.W.P. or P.E.15
Cowden disease (CD) (MIM 158350), or multiple hamartoma syndrome, is a rare autosomal dominant familial cancer syndrome with a high risk of breast cancer. Its clinical features include a wide array of abnormalities but the main characteristics are hamartomas of the skin, breast, thyroid, oral mucosa and intestinal epithelium. The pathognomonic hamartomatous features of CD include multiple smooth facial papules, acral keratosis and multiple oral papillomas1,2. The pathological hallmark of the facial papules are multiple trichilemmomas3. Expression of the disease is variable and penetrance of the dermatological lesions is assumed to be virtually complete by the age of twenty4. Central nervous system manifestations of CD were emphasized only recently and include megalencephaiy, epilepsy and dysplastic gangliocytomas of the cerebellum (Lhermitte-Duclos disease, LDD)5−7. Early diagnosis is important since female patients with CD are at risk of developing breast cancer. Other lesions include benign and malignant disease of the thyroid, intestinal polyps and genitourinary abnormalities4,8−10. To localize the gene for CD, an autosomal genome scan was performed. A total of 12 families were examined, resulting in a maximum lod score of 8.92 at  = 0.02 with the marker D10S573 located on chromosome 10q22−23.
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