title: Four unrelated patients with Lubs X-linked mental retardation syndrome and different Xq28 duplications.
abstract: The Lubs X-linked mental retardation syndrome (MRXSL) is caused by small interstitial duplications at distal Xq28 including the MECP2 gene. Here we report on four novel male patients with MRXSL and different Xq28 duplications delineated by microarray-based chromosome analysis. All mothers were healthy carriers of the duplications. Consistent with an earlier report [Bauters et al. (2008); Genome Res 18: 847-858], the distal breakpoints of all four Xq28 duplications were located in regions containing low-copy repeats (LCRs; J, K, and L groups), which may facilitate chromosome breakage and reunion events. The proximal breakpoint regions did not contain known LCRs. Interestingly, we identified apparent recurrent breakage sites in the proximal and distal breakpoint regions. Two of the four patients displayed more complex rearrangements. Patient 2 was endowed with a quadruplicated segment and a small triplication within the duplication, whereas patient 3 displayed two triplicated segments within the duplication, supporting that the Fork Stalling and Template Switching (FoSTeS) model may explain a subset of the structural rearrangements in Xq28. Clinically, muscular hypertonia and contractures of large joints may present a major problem in children with MRXSL. Because injection of botulinum toxin (BT-A; Botox) proved to be extremely helpful for patient 1, we recommend consideration of Botox treatment in other patients with MRXSL and severe joint contractures.
authors.affiliation: Institut für Humangenetik, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz, Germany. bartsch@humgen.klinik.uni-mainz.de
authors.forename: Oliver
authors.initials: O
authors.lastname: Bartsch
authors.forename: Konstanze
authors.initials: K
authors.lastname: Gebauer
authors.forename: Stanislav
authors.initials: S
authors.lastname: Lechno
authors.forename: Hilde
authors.initials: H
authors.lastname: van Esch
authors.forename: Guy
authors.initials: G
authors.lastname: Froyen
authors.forename: Michael
authors.initials: M
authors.lastname: Bonin
authors.forename: Jörg
authors.initials: J
authors.lastname: Seidel
authors.forename: Barbara
authors.initials: B
authors.lastname: Thamm-Mücke
authors.forename: Denise
authors.initials: D
authors.lastname: Horn
authors.forename: Eva
authors.initials: E
authors.lastname: Klopocki
authors.forename: Christoph
authors.initials: C
authors.lastname: Hertzberg
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zechner
authors.forename: Thomas
authors.initials: T
authors.lastname: Haaf
mesh_terms: D000293:Adolescent; D000328:Adult; D001905:Botulinum Toxins / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D041321:Chromosomes, Human, X; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D009035:Mothers; D010375:Pedigree
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D001905:Botulinum Toxins