Premium
Congenital heart defects in a novel recurrent 22q11.2 deletion harboring the genes CRKL and MAPK1
Author(s) -
Breckpot Jeroen,
Thienpont Bernard,
Bauters Marijke,
Tranchevent LeonCharles,
Gewillig Marc,
Allegaert Karel,
Vermeesch Joris R.,
Moreau Yves,
Devriendt Koenraad
Publication year - 2012
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.35217
Subject(s) - breakpoint , microcephaly , genetics , biology , gene , chromosome , homologous recombination , comparative genomic hybridization , phenotype
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. © 2012 Wiley Periodicals, Inc.