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Molecular genetics of 22q11.2 deletion syndrome
Author(s) -
Morrow Bernice E.,
McDonaldMcGinn Donna M.,
Emanuel Beverly S.,
Vermeesch Joris R.,
Scambler Peter J.
Publication year - 2018
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.40504
Subject(s) - non allelic homologous recombination , genetics , digeorge syndrome , biology , allele , homologous recombination , gene , meiosis , phenotype , homologous chromosome , chromosome , cognition , genetic recombination , neuroscience , recombination
The 22q11.2 deletion syndrome (22q11.2DS) is a congenital malformation and neuropsychiatric disorder caused by meiotic chromosome rearrangements. One of the goals of this review is to summarize the current state of basic research studies of 22q11.2DS. It highlights efforts to understand the mechanisms responsible for the 22q11.2 deletion that occurs in meiosis. This mechanism involves the four sets of low copy repeats (LCR22) that are dispersed in the 22q11.2 region and the deletion is mediated by nonallelic homologous recombination events. This review also highlights selected genes mapping to the 22q11.2 region that may contribute to the typical clinical findings associated with the disorder and explain that mutations in genes on the remaining allele can uncover rare recessive conditions. Another important aspect of 22q11.2DS is the existence of phenotypic heterogeneity. While some patients are mildly affected, others have severe medical, cognitive, and/or psychiatric challenges. Variability may be due in part to the presence of genetic modifiers. This review discusses current genome‐wide efforts to identify such modifiers that could shed light on molecular pathways required for normal human development, cognition or behavior.