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: Oliver Bartsch, Konstanze Gebauer, Stanislav Lechno, Hilde van Esch, Guy Froyen, Michael Bonin, Jörg Seidel, Barbara Thamm-Mücke, Denise Horn, Eva Klopocki, Christoph Hertzberg, Ulrich Zechner, Thomas Haaf
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 152A Issue 2 Pg. 305-12 (Feb 2010) ISSN: 1552-4833 [Electronic] United States
• PMID: 20082459 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright 2010 Wiley-Liss, Inc.

Chemical References

• MECP2 protein, human
• Methyl-CpG-Binding Protein 2
• Botulinum Toxins

Topics

• Adolescent
• Adult
• Botulinum Toxins (therapeutic use)
• Child
• Child, Preschool
• Chromosome Aberrations
• Chromosomes, Human, X
• Female
• Heterozygote
• Humans
• Infant
• Male
• Mental Retardation, X-Linked (genetics)
• Methyl-CpG-Binding Protein 2 (genetics)
• Mothers
• Pedigree