Summary
A de novo interstitial deletion (X)(q27.1q27.3), between the loci DXS 105 and F8, has been found in a mentally retarded female. The deleted X chromosome is preferentially early replicating in fibroblasts, B cells and T cells, suggesting that the missing region plays a role in inactivation of the X chromosome. None of the available DNA probes except DXS 98 maps to the deleted region of about 10000kb. The locus FRAXA is either included in the deletion, or located close to the distal break point.
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Anson DS, Choo KH, Rees DJG, Giannelli F, Gould K, Huddleston JA, Brownlee GG (1984) The gene structure of human anti-haemophilic factor IX. EMBO J 3:1053–1060
Arveiler B, Hofker MH, Bergen AAB, Pearson P, Mandel JL (1987) A PstI RFLP detected by probe cpX73 (DXS 159) in Xq11-q12. Nucleic Acids Res 15:5903
Arveiler B, Oberlé I, Vincent A, Hofker MH, Pearson PL, Mandel JL (1988) Genetic mapping of the Xq27 region: new RFLP markers useful for diagnostic applications in fragile-X and hemophilia-B families. Am J Hum Genet 42:380–389
Balazs J, Purello M, Kurnit DM, Grzeschik K-H, Siniscalco M (1984) Isolation and characterization of human random cDNA clones homologous to DNA from the X chromosome. Somat Cell Mol Genet 10:385–397
Boggs BA, Nussbaum RL (1987) Two anonymous X specific human sequences detecting RFLP in region Xq26-qter. Somat Cell Mol Genet 10:607–613
Boyd Y, Fraser NJ, Craig IW (1988) Specific methylation at the hypervariable DX5 255 locus on active X chromosomes: a simple system for the assessment of X inactivation status. J Med Genet 25:645
Brown WT, Gross AC, Chan CB, Dobkins GS, Jenkins EC (1985) Genetic linkage heterogeneity in the fragile X syndrome. Hum Genet 71:11–18
Brown WT, Wu Y, Gross AC, Chan CB, Dobkin CS, Jenkins EC (1987) RFLP for linkage analysis of fragile X syndrome. Lancet I:280
Camerino G, Mattei MG, Mattei JF, Jaye M, Mandel JL (1983) Close linkage of fragile X-mental retardation syndrome to haemophilia B and transmission through a normal male. Nature 306:701–704
Choo KH, George D, Filby G, Halliday JL, Leversha M, Webb G, Danks DM (1984) Linkage analysis of X-linked mental retardation with and without fragile-X using factor IX gene probe. Lancet II:349
Conley ME, Lavoie A, Briggs C, Brown P, Guerra C, Puck JM (1988) Nonrandom X chromosome inactivation in B cells from carriers of X chromosome-linked severe combined immunodeficiency. Proc Natl Acad Sci USA 85:3090–3094
Davies KE, Young B, Elles R, Hill M, Williamson R (1981) Cloning of a representative genomic library of the human X chromosome after sorting by flow cytometry. Nature 293:379–381
Francke U (1984) Random X inactivation resulting in mosaic mullisomy of region Xp21. 1–p21.3 associated with heterozygosity for ornithine transcarbamylase deficiency and for chronic granulomatous disease. Cytogenet Cell Genet 38:298–307
Fraser NJ, Boyd Y, Brownlee GG, Craig IW (1987) Multiallelic RFLP for M27B, on anonymous single copy genomic clone at Xp11.3-Xcen (DXS 255). Nucleic Acids Res 15:9616
Gitschier J, Wood WJ, Goralka TM, Wion KL, Chen EY, Eaton DH, Vehar GA, Capon DJ, Lawn RM (1984) Characterization of the human factor VIII gene. Nature 312:342–347
Goldman B, Polani PE, Daker MG, Angell RR (1982) Clinical and cytogenetic aspects of X chromosome deletions. Clin Genet 21:36–52
Hamerton J, Holden J, Beckett J, Brasch K, Donald L, McAlpine P, Mulligan L, Partington M, Phillips A, Simpson N, Wang H, White B, Wrogemann K (1982) The isolation and use of cloned X chromosome unique sequences in the study of X-linked disorders. Am J Hum Genet 34:458A
Hofker MH, Bergen AAB, Skraastad MI, Carpenter NJ, Veenema H, Connor JM, Bakker E, Van Ommen GJB, Pearson PL (1987) Efficient isolation of X chromosome-specific singlecopy probes from a cosmid library of a human X/hamster hybrid cell line; mapping of new probes close to the locus for X-linked mental retardation. Am J Med Genet 40:312–328
Jolly DJ, Esty AC, Bernard HU, Friedmann T (1982) Isolation of a genomic clone partially encoding human HPRT. Proc Natl Acad Sci USA 79:5038–5041
Kunkel LM, Tantravali U, Eisenhard M, Latt SD (1982) Regional localization on the human X of DNA sequences cloned from flow sorted chromosomes. Nucleic Acids Res 10:1557–1591
Lyon MF (1961) Gene action in the X chromosome of the mouse (Mus musculus). Nature 190:372–373
Magenis RE, Donlon TA, Canfield WM, Koler R, Bigley R (1984) Partial duplication of X long arm, q26.3-qter: gene dose effects of G6Pd, HPRT, F8 and F9. Cytogenet Cell Genet 37:528
Mandel JL, Arveiler B, Camerino G, Hanauer A, Heilig R, Koenig M, Oberlé I (1986) Genetic mapping of the human X chromosome: linkage analysis of the q26–q28 region that includes the fragile X locus and isolation of expressed sequences. Cold Spring Harb Symp Quant Biol 51:195–203
Marshall Graves JA, Gartler SM (1986) Mammalian X chromosome inactivation: testing the hypothesis of transcriptional control. Somat Cell Mol Genet 12:275–280
Mattei JF, Mattei MG, Giraud F (1983) DNA replication patterns and consequences of translocations between X chromosomes and autosomes. In: Sandberg AA (ed) Cytogenetics of the mammalian X chromosome, vol 3A. Liss, New York, pp 449–469
Mohandas J, Geller RL, Yen PH, Rosendorff J, Bernstein R, Yoshida A, Shapiro LJ (1987) Cytogenetic and molecular studies on a recombinat human X chromosome: implications for the spreading of X chromosome inactivation. Proc Natl Acad Sci USA 84:4954–4958
Patterson M, Kenwrick S, Thibodeau S, Faulk K, Mattei MG, Mattei LF, Davies KE (1987a) Mapping of DNA markers lose to the fragile site on the human X chromosome at Xq27. Nucleic Acids Res 15:2639–2651
Patterson M, Schwartz C, Bell M, Sauer S, Hofker M, Trask B, Engh G van den, Davies KE (1987b) Physical mapping studies on the human X chromosome in the region Xq27-Xqter. Genomics 1:297–306
Persico MG, Viglietto G, Martini G, Toniolo D, Paonessa G, Mesistelli C, Dono R, Vulliamy T, Luzzatto L, D'Urso M (1986) Isolation of human glucose-6-phosphate dehydrogenase (G6PD) cDNA clones: primary structure of the protein and unusual 5′ non-coding region. Nucleic Acids Res 14:2511–2522
Priest JH, Heady JE, Priest RE (1967) Delayed onset of replication of human X chromosomes. J Cell Biol 35:483–487
Riddell DC, Wang HS, Becket J, Chan A, Holden JJA, Mulligan LM, Phillips MA, Simpson NE, Wrogemann K, Hamerston JL, White BN (1986) Regional localization of 18 human X-linked DNA sequences. Cytogenet Cell Genet 42:123–128
Russel LB (1983) X-autosome translocations in the mouse: their characterization and use as tools to investigate gene inactivation and gene action. In: Sandberg AA (ed) Cytogenetics of the mammalian X chromosome, vol 3A. Liss, New York, pp 203–250
Schmidt M, Stolzmann WM (1984) Replication variants of the human inactive X chromosome. II. Frequency and replication rate relative to the other chromosomes of the complement. Chromosome 89:68–75
Schmidt M, Wolf SF, Migeon BR (1985) Evidence for a relationship between DNA methylation and DNA replication from studies of the 5 aze-C-reactivated allocyclic chromosome. Exp Cell Res 158:301–310
Schwartz C, Fitch N, Phelan MC, Richer CL, Stevenson R (1987) Two sisters with a distal deletion at the Xq27 interface: DNA studies indicate that the gene locus for F9 is present. Hum Genet 76:54–57
Skibsted L, Westh H, Niebuhr E (1984) X long-arm deletions. A review of non-mosaic cases studied with banding techniques. Hum Genet 67:1–5
Tabor A, Andersen O, Lundsteen C, Niebuhr E, Sardemann H (1983) Interstitial deletion in the “critical region” of the long arm of the X chromosome in a mentally retarded boy and his normal mother. Hum Genet 64:196–199
Tantravali U, Kirschmer DA, Beouregard L, Page L, Kunkel L, Latt S (1983) Cytological and molecular analysis of 46,XXq-cells to identify a DNA segment that might serve as a probe for a putative human X chromosome inactivation center. Hum Genet 64:33–38
Trunca C, Therman E, Rosenwaks Z (1984) The phenotypic effects of small distal Xq deletions. Hum Genet 68:87–89
Van Ommen GJB, Arnberg AC, Baas F, Brocas H, Sterk A, Tegelaers WHH, Vassart G, Vijlder JJM de (1983) The human thyroglobulin gene contains two 15–17 kb introns near its 3′ end. Nucleic Acids Res 11:2273–2285
Willard HF (1977) Tissue-specific heterogeneity in DNA replication patterns of human X chromosomes. Chromosoma 61:61–73
Willard HF, Breg WR (1980) Human X chromosomes: synchrony of DNA replication in diploid and triploid fibroblasts with multiple active or inactive X chromosomes. Somat Cell Genet 6:187
Wolf SF, Jolly DJ, Lunnen KD, Friedmann T, Migeon BR (1984) Methylation of the HPRT locus on the human X chromosome: implications for X chromosome inactivation. Proc Natl Acad Sci USA 81:2806–2810
Yen PH, Patel P, Craig Chinault A, Mohandas T, Shapiro LJ (1984) Differential methylation of HPRT genes on active and inactive human X chromosome. Proc Natl Acad Sci USA 81:1759–1763
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Schmidt, M., Certoma, A., Du Sart, D. et al. Unusual X chromosome inactivation in a mentally retarded girl with an interstitial deletion Xq27: implications for the fragile X syndrome. Hum Genet 84, 347–352 (1990). https://doi.org/10.1007/BF00196232
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DOI: https://doi.org/10.1007/BF00196232