Congenital heart defects in a novel recurrent 22q11.2 deletion harboring the genes CRKL and MAPK1.
The proximal region of the long arm of chromosome 22 is rich in low copy repeats (LCR). Non-allelic homologous recombination (NAHR) between these substrates explains the high prevalence of recurrent rearrangements within this region. We have performed array comparative genomic hybridization in a normally developing girl with growth delay, microcephaly, and truncus arteriosus, and have identified a novel recurrent 22q11 deletion that spans LCR22-4 and partially affects the common 22q11.2 deletion syndrome and the distal 22q11 deletion syndrome. This deletion is atypical as it did not occur by NAHR between any of the major LCRs found on 22q11.2. However, the breakpoint containing regions coincide with highly homologous regions. An identical imbalance was reported previously in a patient with striking phenotypic similarity. Computational gene prioritization methods and biological evidence denote the genes CRKL and MAPK1 as the highest ranking candidates for causing congenital heart disease within the deleted region.
Center for Human Genetics, University Hospitals Leuven, Herestraat, Leuven, Belgium.
Jeroen
J
Breckpot
Bernard
B
Thienpont
Marijke
M
Bauters
Leon-Charles
LC
Tranchevent
Marc
M
Gewillig
Karel
K
Allegaert
Joris R
JR
Vermeesch
Yves
Y
Moreau
Koenraad
K
Devriendt
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22; D005260:Female; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D007223:Infant; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; C082869:CRKL protein; D009687:Nuclear Proteins; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1