Warsaw breakage syndrome, a cohesinopathy associated with mutations in the XPD helicase family member DDX11/ChlR1.

Abstract

The iron-sulfur-containing DNA helicases XPD, FANCJ, DDX11, and RTEL represent a small subclass of superfamily 2 helicases. XPD and FANCJ have been connected to the genetic instability syndromes xeroderma pigmentosum and Fanconi anemia. Here, we report a human individual with biallelic mutations in DDX11. Defective DDX11 is associated with a unique cellular phenotype in which features of Fanconi anemia (drug-induced chromosomal breakage) and Roberts syndrome (sister chromatid cohesion defects) coexist. The DDX11-deficient patient represents another cohesinopathy, besides Cornelia de Lange syndrome and Roberts syndrome, and shows that DDX11 functions at the interface between DNA repair and sister chromatid cohesion.

• Authors: Petra van der Lelij, Krystyna H Chrzanowska, Barbara C Godthelp, Martin A Rooimans, Anneke B Oostra, Markus Stumm, Małgorzata Z Zdzienicka, Hans Joenje, Johan P de Winter
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 86 Issue 2 Pg. 262-6 (Feb 12 2010) ISSN: 1537-6605 [Electronic] United States
• PMID: 20137776 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Chemical References

• DNA Helicases
• DDX11 protein, human
• DEAD-box RNA Helicases

Topics

• Abnormalities, Multiple (enzymology, genetics)
• Adolescent
• Base Sequence
• Child, Preschool
• Chromosome Breakage
• DEAD-box RNA Helicases (deficiency, genetics)
• DNA Helicases (deficiency, genetics)
• DNA Mutational Analysis
• Female
• Humans
• Infant
• Infant, Newborn
• Male
• Molecular Sequence Data
• Mutation (genetics)
• Neoplasms (genetics)
• Pedigree
• Phenotype
• Poland
• Pregnancy
• Sister Chromatid Exchange (genetics)
• Syndrome
• Xeroderma Pigmentosum (genetics)