title: 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.
authors.affiliation: National Centre of Mental Health, Russian Academy of Medical Sciences, 113152, Zagorodnoe sh. 2, Moscow, Russia. yurov@rcmh.msk.ru
authors.forename: Y B
authors.initials: YB
authors.lastname: Yurov
authors.forename: S G
authors.initials: SG
authors.lastname: Vorsanova
authors.forename: A D
authors.initials: AD
authors.lastname: Kolotii
authors.forename: I Y
authors.initials: IY
authors.lastname: Iourov
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods*; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007223:Infant; D007231:Infant, Newborn; D008214:Lymphocytes / Q000166:cytology; D009154:Mutation / Q000235:genetics*; D015518:Rett Syndrome / Q000097:blood / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics*