Summary
Pembrey et al. (1985) proposed a hypothesis regarding the nature of the fragile X [fra(X)] mutation. Recently they analyzed DNA linkage data (Winter and Pembrey 1986) that we and others have published on fra(X) pedigrees, found significant linkage heterogeneity, and modified their hypothesis to explain the observations. We would like to point out that their modified hypothesis is not supported by the data available.
This is a preview of subscription content, log in via an institution to check access.
References
Brown WT, Jenkins E, Friedman E, Chan C, Wolf E, Brooks J, Cohen I, Wisniewski K, French J (1984) Genetic heterogeneity in fragile X. Am J Hum Genet 36:4:46S (abstr)
Brown WT, Gross AC, Chan CB, Jenkins EC (1985) Genetic linkage heterogeneity in the fragile X syndrome. Hum Genet 71:11–18
Brown WT, Gross AC, Chan CB, Jenkins EC (1986) DNA linkage studies in the fragile X syndrome suggest genetic heterogeneity. Am J Med Genet 23:643–664
Brown WT, Jenkins EC, Gross AC, Chan CB, Krawczun MS, Duncan CJ, Sklower SL, Fisch GS (1987) Further evidence for genetic heterogeneity in the fragile X syndrome. Hum Genet 75 (in press)
Camerino G, Mattei MG, Mattei JF, Jaye M, Mandel JL (1983) Close linkage of fragile X linked mental retardation syndrome to haemophilia B and transmission through a normal male. Nature 306:701–707
Davies KE, Mattei MG, Mattei JF, Veenema H, McGlade S, Harper K, Tommerup N, Nielsen KB, Mikkelsen M, Beighton P, Drayna D, White R, Pembrey ME (1985) Linkage studies of X-linked mental retardation: high frequency of recombination in the telomeric region of the human X chromosome. Hum Genet 70: 249–255
Drayna D, White R (1985) The genetic linkage map of the human X chromosome. Science 230:753–758
Nussbaum RL, Airhart SD, Ledbedder DH (1986) Recombination and amplification of pyrimidine-rich sequences may be responsible for initiation and progression of the Xq27 fragile site: a hypothesis. Am J Med Genet 23:715–721
Oberle I, Heilig R, Moisan JP, Kliepfer C, Mattei MG, Mattei JF, Boue J, Froster-Iskenius U, Jacobs PA, Lathrop GM, Lalouel JM, Mandel JL (1986) Genetic analysis of the fragile X mental retardation syndrome with two flanking polymorphic DNA markers. Proc Natl Acad Sci (USA) 83:1016–1020
Pembrey ME, Winter RM, Davies KE (1984) A premutation that generates the definite mutation by recombination explains the inheritance of the Martin Bell syndrome (fragile X). J Med Genet 21:299 (abstr)
Pembrey ME, Winter RM, Davies KE (1985) A premutation that generates a defect at crossing-over explains the inheritance of fragile X mental retardation. Am J Med Genet 21:709–717
Sherman SL, Morton NE, Jacobs PA, Turner G (1984) The marker (X) syndrome: a cytogenetic and genetic analysis. Ann Hum Genet 48:21–37
Sherman SL, Jacobs PA, Morton NE, Froster-Iskenius U, Howard-Peebles PN, Nielsen KB, Partington MW, Sutherland GR, Turner G, Watson M (1985) Further segregation analysis of the fragile X syndrome with special reference to transmitting males. Hum Genet 69:289–299
Winter RM, Pembrey ME (1986) Analysis of linkage relationships between genetic markers around the fragile X locus with special reference to the daughters of normal transmitting males. Hum Genet 74:93–97
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Brown, W.T., Sherman, S.L. & Dobkin, C.S. Hypothesis regarding the nature of the fragile X mutation. Hum Genet 75, 294–295 (1987). https://doi.org/10.1007/BF00281078
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00281078