Warsaw breakage syndrome, a cohesinopathy associated with mutations in the XPD helicase family member DDX11/ChlR1.
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.
van der Lelij
Petra
P
Department of Clinical Genetics, VU University Medical Center, Van der Boechorststraat 7, Amsterdam, The Netherlands.
Chrzanowska
Krystyna H
KH
Godthelp
Barbara C
BC
Rooimans
Martin A
MA
Oostra
Anneke B
AB
Stumm
Markus
M
Zdzienicka
Małgorzata Z
MZ
Joenje
Hans
H
de Winter
Johan P
JP
D000015:Abnormalities, Multiple / Q000201:enzymology* / Q000235:genetics*; D000293:Adolescent; D001483:Base Sequence; D002675:Child, Preschool; D019457:Chromosome Breakage; D053487:DEAD-box RNA Helicases / Q000172:deficiency / Q000235:genetics*; D004265:DNA Helicases / Q000172:deficiency / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D011044:Poland; D011247:Pregnancy; D012854:Sister Chromatid Exchange / Q000235:genetics*; D013577:Syndrome; D014983:Xeroderma Pigmentosum / Q000235:genetics*
D004265:DNA Helicases; C101830:DDX11 protein, human; D053487:DEAD-box RNA Helicases