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Relationship between age and mental status and the expression of the fragile(x) in heterozygotes for the martin-bell syndrome

Departamento de Biologia, Instituto de Biociências, USP, Caixa Postal 11461, 05499 São Paulo, SP, Brasil

Leda Navajas; Angela M. Vianna-Morgante

ABSTRACT

We analyzed 547 female relatives of Martin-Bell syndrome patients, 50 from our laboratory and 497 from the literature. Approximately 50% of the obligate heterozygotes were detected cytogenetically by manifestation of the fra(X). Mental impairment and age of normal heterozygotes were found to affect the fra(X) expression. The estimated frequency of mental impairment in heterozygous female sibs of affected males was 48.5%.

Keywords: age; mental; expression; fragile(x); heterozygotes; martin-bell; syndrome.

REFERENCES

Brookwell, R., Daniel, A., Turner, G. and Fishburn, J. (1982). The fragile X(g27) form of X-linked mental retardation: FUdR as an inducing agent for fra(X) (q27) expression in lymphocytes. Am. J. Med. Genet. 13 : 139-148.

Camerino, G., Mattei, M.G., Mattei, J.F., Jaye, M. and Mandel, J.L. (1983). Close linkage of fragile-X mental retardation syndrome to haemophilia B and transmission through a normal male. Nature 30: 701-704.

Carpenter, N.J., Leichtman, L.G. and Say, B. (1982). Fragile X-linked mental retardation. A survey of 65 patients with mental retardation of unknown origin. Am. J. Dis. Child. 136: 392-398.

Chudley, A.E., Knoll, J., Gerrard, J.W., Shepel, L., McGahey, E. and Anderson, J. (1983). Fragile (X) X-linked mental retardation. I. Relationship between age and intelligence and the frequency of expression of fragile (X) (q28). Am. J. Med. Genet. 14: 669-712.

Dunn, H.G., Renpenning, H., Gerrard, J.W., Miller, J.R., Tabata, T. and Federoff, S. (1963). Mental retardation as a sex-linked defect. Am. J. Mental Def. 67: 827-848.

Fishburn, J., Turner, G., Daniel, A. and Brookwell, R. (1983). The diagnosis and frequency of X- linked conditions in a cohort of moderately retarded males with affected brothers. Am. J. Med. Genet. 14: 713-724.

Froster-Iskenius, U., Schulze, A. and Schwinger, E. (1984). Transmission of the marker X syndrome trait by unaffected males: conclusions from studies of large families. Hum. Genet. 67: 419-427.

Fryns, J.P. (1984). The fragile X syndrome. A study of 83 families. Clin. Genet. 26: 497-528.

Fryns, J.P. and van den Berghe, H. (1983). X-linked mental retardation and fragile (Xq27) site. Clin. Genet. 23 : 203-206.

Gardner, R.J.M., Smart, R.D., Cornell, J.M., Merckel, L.M. and Beighton, P. (1983). The fragile X chromosome in a large Indian kindred. Clin. Genet. 23: 31.1-317.

Gustavson, K.H., Holmgren, G., Blomquist, H.K., Mikkelsen, M., Nordenson, I., Poulden, H. and Tommerup, N. (1981). Familial X-linked mental retardation and fragile X chromosomes in two Swedish families. Clin. Genet. 19: 101-110.

Hecht, J.T., Scott, C.I., Butler, I.J. and Moore, C.M. (1983). X-linked mental retardation with fragile site at band Xq2800. Lancet I: 986.

Herbst, D.S., Dunn, H.G., Dill, F.J., Kalousek, D.K. and Krywaniuk, I.W. (1981). Further delineation of X-linked mental retardation. Hum. Genet. 58: 366-372.

Howard-Peebles, P.N. (1980). Fragile sites in human chromosomes. II: Demonstration of the fragile site Xq27 in carriers of X-linked mental retardation. Am. J. Med. Genet. 7: 497-501.

Howard-Peebles, P.N. and Stoddard, G.R. (1979). X-linked mental retardation with macroorchidism and marker X chromosomes. Genetics 50: 247-251.

Howard-Peebles, P.N., Stoddard, G.R. and Mims, M.G. (1979). Familial X-linked mental retarda- tion, verbal disability and marker X chromosomes. Am. J. Hum. Genet. 31: 214-222.

Jacobs, P.A., Glover, T.W., Mayer, M., Fox, P., Gerrard, J.W., Dunn, H.G. and Herbst, D.S. (1980). X-linked mental retardation: a study of 7 families. Am. J. Med. Genet. 7: 471-489.

Jacobs, P.A., Mayer, M., Matsuura, J., Rhoads, F. and Yee, S.C. (1983). A cytogenetic study of a population of mentally retarded males with special reference to the marker (X) Syndrome. Hum. Genet. 63 : 139-148.

Kähkönen, M., Leisti, J., Wilska, M. and Varonen, S. (1983). Marker X-associated mental retardation. A study of 150 retarded males. Clin. Genet. 23: 397-404.

Lubs, H.A. (1969). A marker X-chromosome. Am. J. Hum. Genet. 21: 231-244.

Lubs, H., Travers, H., Lujan, E. and Carroll, A. (1984). A large kindred with X-linked mental retardation marker X and macroorchidism. Am. J. Med. Genet. 17: 145-157.

Martin, R.H., Lin, C.C., Mathies, B.J. and Lowry, R.B. (1980). X-linked mental retardation with macroorchidism and marker-X chromosomes. Am. J. Med. Genet. 7: 433-441.

Mattei, J.F., Mattei, M.G., Aumeras, C., Auger, M. and Giraud, F. (1981). X-linked mental retardation with the fragile X. A study of 15 families. Hum. Genet. 59: 281-289.

Miezejeski, C.M., Jenkins, E.C., Hill, A.L., Wisniewski, K. and Brown, W.T. (1984). Letter to the editor: Verbal vs nonverbal ability, fragile X syndrome and heterozygous carriers. Am. J. Hum. Genet. 36: 227-229.

Nielsen, K.B., Tommerup, N., Poulsen, H., Jacobsen, P., Beck, B. and Mikkelsen, M. (1983). Carrier detection and X-inactivation studies in the Fragile X syndrome. Cytogenetic studies in 63 obligate and potential carriers of the fragile X. Hum. Genet. 64: 240-245.

Nielsen, K.B., Tommerup, N., Poulsen, H. and Mikkelsen, M. (1981). X-linked mental retardation with fragile X: a pedigree showing transmission by apparently unaffected males and partial expression in female carriers. Hum. Genet. 59:23-25.

Rhoads, F.A., Oglesby, A.D., Mayer, M. and Jacobs, P.A. (1982). Marker X syndrome in an oriental family with probable transmission by a normal male. Am. J. Med. Genet. 12: 205217.

Schmidt, A. (1982). Fragile site Xq27 and mental retardation. Clinical and cytogenetic manifestation in heterozygotes and hemizygotes of five kindreds. Hum. Genet. 60: 322-327.

Sherman, S.L., Jacobs, P.A., Morton, N.E., Froster-Iskenius, U., Howard-Peebles, P.N., Nielsen, K.B., Partington, M.W., Sutherland, G.R., Turner, G. and Watson, M. (1985). Further segregation analysis of the fragile X syndrome with special reference to transmitting males. Hum. Genet. 69: 289-299.

Sherman, S.L., Morton, N.E., Jacobs, P.A. and Tuner, G. (1984). The marker (X) syndrome: a cytogenetic and genetic analysis. Ann. Hum. Genet. 48:21-37.

Sherman, S.L., Turner, G., Robinson, H. and Laing, S. (1988). Investigation of the segregation of the fragile X mutation in daughters of obligate carrier women. Am. J. Med. Genet. 30: 633639.

Soares, V.R.X., Rosenberg, C., Vianna-Morgante, A.M. and Navajas, L. (1988). Normal male carriers of the Martin-Bell syndrome gene: implications for genetic counseling. Rev. Bras. Genet. II: 769-781.

Sutherland, G.R. (1977). Marker X chromosomes and mental retardation. N. Engl. J. Med. 296: 1415.

Sutherland, G.R. (1978). Carrier detection in X-linked mental retardation. Med. J. Aust. 2:624. Sutherland, G.R. (1979a). Heritable fragile sites on human chromosomes. I. Factors affecting expression in lymphocyte culture. Am. J. Hum. Genet. 31: 125-135.

Sutherland, G.R. (1979b). Heritable fragile sites on human chromosomes. II. Distribution, phenotypic effects, and cytogenetics. Am. J. Hum. Genet. 31: 136-148.

Sutherland, G.R. (1979c). Heritable fragile sites on human chromosomes. III. Detection of fra(X) (q27) in males with X-linked mental retardation and in their female relatives. Hum. Genet. 53:23-27.

Sutherland, G.R. (1980). Experience with fra(X) (q27) in retarded males and carrier females. Clin. Genet. 17:89.

Turner, G., Brookwell, R., Daniel, A., Selikowitz, M.B. and Zilibowitz, M. (1980). Heterozygous expression of X-linked mental retardation and the marker X. New Engl. J. Med. 303: 662664.

Turner_ G. and Jacohs_ P_ (19831. Marker (Xl-linked mental retardation. Adv. Hum_ Genet_ 13:

Uchida, I.A. and Joyce, E.M. (1982). Activity of the fragile X in heterozygous carriers. Am. J. Hum. Genet. 34 (2) : 286-293.

Van Roy, B.C., Smedt, M.C., Raes, R.A., Dumon, J.E. and Leroy, J.G. (1983). Fragile X trait in a large kindred: transmission also through normal males. J. Med. Genet. 20: 286-289.

Webb, T., Thake, A. and Todd, J. (1986). Twelve families with fragile X(827). J. Med. Genet. 23: 400-406.