title: Partial Xp duplication in a girl with dysmorphic features: the change in replication pattern of late-replicating dupX chromosome.
abstract: In this paper we present the case of a girl at the age of 32 months with dysmorphic features, including general muscular hypotonia, developmental delay and mental retardation. The cytogenetic analysis revealed de novo partial duplication of Xp: 46,X,dup(X)(p11.23-->p22.33: :p11.23-->p22.33). To characterize the duplication, X painting, Kallman (KAL), yeast artificial chromosomes (YACs) and bacterial artificial chromosomes (BACs) covering Xp11.23-->Xp22.33 region were used. Selective inactivation of the abnormal X chromosome using HpaII digestion of the AR gene was evident. After BrdU incorporation the abnormal X was late-replicating in all lymphocytes examined. There was one peculiar exception observed: the break-point region was consistently early replicating. The replicating pattern of this region corresponded to the active X chromosome. Methylation pattern of late replicating X chromosome was studied also using antibodies against 5-methylcytosine. The pattern corresponded to the normally inactive X chromosome, with the exception of the previously observed break-point region which revealed an early replicating pattern with strong fluorescent signal, similar to the pattern of the active X chromosome. The observed phenomenon could lead to the abnormal phenotype of the patient, with some normally inactive genes of the break-point region escaping the inactivation process. The abnormal clinical findings could also be due to tissue-dependent differences in the inactivation pattern.
authors.affiliation: Maribor Teaching Hospital, Laboratory of Medical Genetics, Maribor, Slovenia. nadja.kokalj-vokac@sb-mb.si
authors.forename: N
authors.initials: N
authors.lastname: Kokalj Vokac
authors.forename: P
authors.initials: P
authors.lastname: Seme Ciglenecki
authors.forename: A
authors.initials: A
authors.lastname: Erjavec
authors.forename: B
authors.initials: B
authors.lastname: Zagradisnik
authors.forename: A
authors.initials: A
authors.lastname: Zagorac
mesh_terms: D002675:Child, Preschool; D002869:Chromosome Aberrations; D019175:DNA Methylation; D004261:DNA Replication; D002658:Developmental Disabilities / Q000150:complications / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D005260:Female; D020440:Gene Duplication; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics*; D008297:Male; D009123:Muscle Hypotonia / Q000150:complications / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012729:Sex Chromosome Aberrations; D014960:X Chromosome / Q000235:genetics*