Abstract
Epidermolytic palmoplantar keratosis (EPPK) cosegregates with breast and ovarian cancers in a large French pedigree, raising the possibility that a single genetic mutation might cause these conditions and offering a potential lead to the identification of a hereditary breast/ovarian cancer gene. We have performed linkage analysis and show that the EPPK locus lies on the long arm of chromosome 17 near the type I keratin gene cluster and the proposed breast cancer gene (BRCA1). The type I keratin 9 gene has been partially sequenced in four affected individuals. A single base mutation within the rod domain of the protein cosegregates with EPPK in all affected individuals tested. Although inheritance of this mutation is likely responsible for EPPK, it is unlikely to be the cause of the breast and ovarian cancer.
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References
Coulombe, J. et al. Point mutations in human keratin 14 genes of epidermolysis bullosa simplex patients: Genetic and functional analysis. Cell 66, 1301–1311 (1991).
Lane, E.B. et al. A mutation in the conserved helix termination peptide of keratin 5 in hereditary skin blistering. Nature 356, 2444–2446 (1993).
Hovnanian, A. et al. A missense mutation in the rod domain of keratin 14 associated with recessive epidermolysis bullosa simplex. Nature Genet. 3, 327–332 (1993).
Rothnagel, J.A. et al. Mutations in the rod domain of keratins 1 and 10 in epidermolytic hyperkeratosis. Science 257, 1128–1130 (1992).
Cheng, J. et al. The genetic basis of epidermolytic hyperkeratosis: A disorder of differentiation-specific epidermal keratin genes. Cell 70, 811–819 (1992).
Chipev, C.C. et al. A leucine-proline mutation in the H11 subdomain of keratin 1 causes epidermolytic hyperkeratosis. Cell 70, 821–828 (1992).
Letai, A. et al. Disease severity correlates with position of keratin point mutations in patients with epidermolysis bullosa simplex. Proc. natn. Acad. Sci. U.S.A. 90, 3197–3201 (1993).
Klaus, S., Weinstein, GD. & Frost, P. Localized epidermolytic hyperkeratosis. A form of keratoderma of the palms and soles. Arch. Dermatol. 101, 272–275 (1970).
Reis, A., Küster, W., Eckhardt, R. & Sperling, K. Mapping of a gene for epidermolytic palmoplantar keratoderma to the region of the acidic keratin gene cluster at 17q12–21. Hum. Genet. 90, 113–116 (1992).
Knapp, A.C. et al. Cytokeratin No.9, an epidermal type I keratin characteristic of a special program of keratinocyte differentiation displaying body site specificity. J. cell Biol. 103, 657–667 (1986).
Moll, I., Heid, H., Franke, W.W. & Moll, R. Distribution of a special subset of keratinocytes characterized by the expression cytokeratin 9 in adult and fetal human epidermis of various body sites. Differentiation 33, 254–265 (1987).
Langbein, L., Heid, H.W., Moll, I. & Franke, W.W. Molecular characterization of the body site-specific human epidermal cytokeratin 9: cDNA cloning, amino acid sequence, and tissue specificity of gene expression. Differentiation (in the press).
Anderson, L.A. et al. High-density genetic map of the BRCA1 region of chromosome 17q12–21. Genomics 17, 618–623 (1993).
Simard, J. et al. Genetic mapping of the breast-ovarian cancer syndrome to a small interval on chromosome 17q12–21: Exclusion of candidate genes EDH17B2 and RARA. Hum. molec. Genet. 2, 1193–1199 (1993).
Lynch, H.T. Genetics and breast cancer. (Van Nostrand Reinhold, New York, 1981).
Go, R.C.P. et al. Genetic epidemiology of breast cancer and associated cancers in high risk families. I. Segregation analysis. JNCI 71, 455–461 (1983).
Hall, J.M., Lee, M.K., Morrow, J., Anderson, L. & King, M.-C. Linkage of early onset familial breast cancer to chromosome 17q21. Science 250, 1684–1689 (1990).
Narod, S.A. et al. Familial breast-ovarian cancer locus on chromosome 17q12–23. Lancet 338, 82–83 (1991).
Easton, D.F., Bishop, D.T., Ford, D., Crockford, G.P. & Genetic linkage analysis in familial breast and ovarian cancer: Results from 214 families. Am. J. hum. Genet. 52, 678–701 (1993).
Blanchet-Bardon, C. et al. Hereditary epidermolytic palmoplantar keratoderrna associated with breast and ovarian cancer in a large kindred. Br. J. Dermatol. 117, 363–370 (1987).
Bowcock, A.M. et al. THRA1 and D17S183 flank an Interval of <4cM. Am. J. hum. Genet. 52, 718–722 (1993).
Feunteun, J. et al. A breast-ovarian cancer susceptibility gene maps to chromosome 17q21. Am. J. hum. Genet. 52, 736–742 (1993).
Howel-Evans, W., McConnel, R.B., Clarke, C.A. & Sheppard, P.M. Carcinoma of the oesophagus with keratosis palmaris et plantaris (tylosis). A study of two families. Q. J. Med. 27, 413–429 (1958).
Bennion, S.D. & Patterson, J.W. Keratosis punctata palmaris and plantaris and adenocarcinoma of the colon. J. Am. Acad. Dermatol. 10, 587–591 (1984).
Newman, B., Austin, M.A., Lee, M. & King, M.-C. Inheritance of human breast cancer evidence for autosomal dominant transmission in high-risk families. Proc. natn. Acad. Sci. U.S.A. 85, 3044–3048 (1988).
Claus, E.B., Risch, N. & Thompson, W.D. Genetic analysis of breast cancer in the cancer and steroïd hormone study. Am. J. hum. Genet. 48, 232–242 (1991).
Schildkraut, J.M. & Thompson, W.D. Familial ovarian cancer: a population-based case-control study. Am. J. Epidemiol. 128, 456–466 (1988).
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Torchard, D., Blanchet-Bardon, C., Serova, O. et al. Epidermolytic palmoplantar keratoderma cosegregates with a keratin 9 mutation in a pedigree with breast and ovarian cancer. Nat Genet 6, 106–110 (1994). https://doi.org/10.1038/ng0194-106
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DOI: https://doi.org/10.1038/ng0194-106
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