Advertisement

Molecular-cytogenetic investigation of skewed chromosome X inactivation in Rett syndrome

      Abstract

      We have developed an approach to differentiate homologous X chromosomes in metaphase chromosomes and interphase nuclei by a fluorescence in situ hybridization (FISH) technique with chromosome X-specific alpha-satellite DNA probe. FISH analysis of metaphase chromosomes in a cohort of 33 girls with Rett syndrome (RTT) allowed us to detect eight girls with structurally different X chromosomes, one X chromosome with a large and another one with a small centromeric heterochromatin (so-called chromosomal heteromorphism). Step-wise application of differential replication staining and the FISH technique to identify the inactivation status of paternal and maternal chromosome X in RTT girls was applied. Skewed X inactivation in seven RTT girls with preferential inactivation of one X chromosome over the other X chromosome was detected in 62–93% of cells. Therefore, non-random or skewed X inactivation with variable penetrance in blood cells could take place in RTT.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Brain and Development
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Willard H.F.
        • Waye J.S.
        Hierarchical order in chromosome-specific human alpha satellite DNA.
        Trends Genet. 1987; 3: 192-198
        • Alexandrov I.A.
        • Mitkevich S.P.
        • Yurov Y.B.
        The phylogeny of human chromosome specific alpha satellites.
        Chromosoma. 1988; 96: 443-453
        • Yurov Y.B.
        • Mitkevich S.P.
        • Alexandrov I.A.
        Application of cloned satellite DNA sequences to molecular-cytogenetic analysis of constitutive heterochromatin in man.
        Hum Genet. 1987; 76: 157-164
        • Yurov Y.B.
        • Selivanova H.A.
        • Deryagin G.V.
        Use of cloned alpha satellite DNA probes for the analysis of polymorphic heterochromatic regions of human chromosomes and parental origin of trisomy 21 (in Russian).
        Genetica. 1991; 27: 1637-1647
        • Yurov Y.B.
        • Soloviev I.V.
        • Vorsanova S.G.
        • Marcais B.
        • Roizes G.
        • Lewis R.
        High resolution fluorescence in situ hybridization using cyanine and fluorescein dyes: ultra-rapid chromosome detection by directly fluorescently labelled alphoid DNA probes.
        Hum Genet. 1996; 97: 390-398
        • Latt S.A.
        Microfluorometric detection of deoxyribonucleic acid and replication in human metaphase chromosomes.
        Proc Natl Acad Sci USA. 1973; 70: 3395-3399
        • Hagberg B.
        Rett syndrome: recent clinical and biological aspects.
        in: Arzimanoglou A. Goutieres F. Trends in child neurology. John Libbey Eurotext, Paris1996: 143-146
        • Vorsanova S.G.
        • Demidova I.A.
        • Ulas V.Y.
        • Soloviev I.V.
        • Kazantszeva L.Z.
        • Yurov Y.B.
        Cytogenetic and molecular-cytogenetic investigation of Rett syndrome: analysis of 31 cases.
        NeuroReport. 1996; 8: 187-189
        • Vorsanova S.G.
        • Demidova I.A.
        • Ulas V.Y.
        • Soloviev I.V.
        • Kravets V.S.
        • Kazantzeva L.Z.
        • Yurov Y.
        Cytogenetic and molecular-cytogenetic diagnosis of Rett syndrome in children (in Russian).
        Korsakov's J Neurol Psychiatry. 1998; 4: 53-56
        • Kormann-Bortolotto M.H.
        • Woods C.G.
        • Green S.H.
        • Webb T.
        X-inactivation in girls with Rett syndrome.
        Clin Genet. 1992; 42: 296-301
        • Webb T.
        • Watkiss E.
        • Woods C.G.
        Neither uniparental disomy nor skewed X-inactivation explains Rett syndrome.
        Clin Genet. 1993; 44: 236-240
        • Webb T.
        • Watkiss E.
        A comparative study of X-inactivation in Rett syndrome probands and control subjects.
        Clin Genet. 1996; 49: 189-195
        • Camus P.
        • Abbadi N.
        • Perrier M.-C.
        • Chery M.
        • Gilgenkrantz S.
        X chromosome inactivation in 30 girls with Rett syndrome: analysis using the probe.
        Hum Genet. 1996; 97: 247-250
        • Zoghbi H.Y.
        • Percy A.K.
        • Schultz R.J.
        • Fill C.
        Pattern of X chromosome inactivation in the Rett syndrome.
        Brain Dev. 1990; 12: 131-135
        • Allen R.C.
        • Zoghby H.Y.
        • Moseley A.B.
        • Rosenblatt H.M.
        • Belmont J.W.
        Methylation of HpaII and HhaI sites near polymorphic CAG repeat in the human androgen-receptor gene correlate with X chromosome inactivation.
        Am J Hum Genet. 1992; 51: 1229-1239
        • Schanen C.
        • Franke U.
        A severely affected male born into Rett syndrome kindred supports X-linked inheritance and allows extension of the exclusion map.
        Am J Hum Genet. 1998; 63: 267-269
        • Siranni N.
        • Naidu S.
        • Pereira J.
        • Pilotto R.F.
        • Hoffman E.P.
        Rett syndrome: confirmation of X-linked dominant inheritance, and localization of the gene to Xq28.
        Am J Hum Genet. 1998; 63: 1552-1558
        • Amir R.E.
        • Van den Veyver I.B.
        • Wan M.
        • Tran C.Q.
        • Franke U.
        • Zoghby H.Y.
        Rett syndrome is caused by mutations in X-linked MeCP2, encoding methyl-CpG-binding protein 2.
        Nat Genet. 1999; 23: 185-188
        • Wan M.
        • Sung Jae Lee S.
        • Zhang X.
        • Houwink-Manville I.
        • Song H.-R.
        • Amir R.E.
        • et al.
        Rett syndrome and beyond: recurrent spontaneous and familial MeCP2 mutations at CpG hotspots.
        Am J Hum Genet. 1999; 65: 1520-1529