Lack of X inactivation associated with maternal X isodisomy: Evidence for a counting mechanism prior to X inactivation during human embryogenesis

Journal Article · Mon Jan 01 04:00:00 EST 1996 · American Journal of Human Genetics

OSTI ID:232384

Migeon, B R; Torchia, B S; Fu, S ^[1]

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1. Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States); and others

We have previously reported functional disomy for X-linked genes in females with tiny ring X chromosomes and a phenotype significantly more abnormal than Turner syndrome. In such cases the disomy results from failure of these X chromosomes to inactivate because they lack DNA sequences essential for cis X inactivation. Here we describe a novel molecular mechanism for functional X disomy that is associated with maternal isodisomy. In this case, the severe mental retardation and multiple congenital abnormalities in a female with a mosaic 45,X/46,X,del(X) (q21.3-qter)/46X,r(X) karyotype are associated with overexpression of the genes within Xpter to Xq21.31 in many of her cells. Her normal X, ring X, and deleted linear X chromosomes originate from the same maternal X chromosome, and all are transcriptionally active. None expresses X inactive specific transcript (XIST), although the locus and region of the putative X inactivation center (XIC) are present on both normal and linear deleted X chromosomes. To our knowledge, this is the first report of a functional maternal X isodisomy, and the largest X chromosome to escape inactivation. In addition, these results (1) show that cis inactivation does not invariably occur in human females with two X chromosomes, even when the XIC region is present on both of them; (2) provide evidence for a critical time prior to the visible onset of X inactivation in the embryo when decisions about X inactivation are made; and (3) support the hypothesis that the X chromosome counting mechanism involves chromosomal imprinting, occurs prior to the onset of random inactivation, and is required for subsequent inactivation of the chromosome. 41 refs., 4 figs., 2 tabs.

• OSTI ID: 232384
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 1 Vol. 58; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CHROMOSOMAL ABERRATIONS
CLONE CELLS
CONGENITAL MALFORMATIONS
DNA HYBRIDIZATION
DNA SEQUENCING
FEMALES
FLUORESCENCE
GENE REGULATION
GENES
GENETIC MAPPING
GENOTYPE
HUMAN X CHROMOSOME
HYBRIDIZATION
KARYOTYPE
MENTAL DISORDERS
ONTOGENESIS
PHENOTYPE
POLYMERASE CHAIN REACTION
RING CHROMOSOMES
STRUCTURE-ACTIVITY RELATIONSHIPS
TRANSCRIPTION