Molecular genetics of 22q11.2 deletion syndrome
Year: 2018
Type: review
Abstract: 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.
DOI: 10.1002/ajmg.a.40504
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: Fondation Jérôme Lejeune, British Heart Foundation, Fondation Leducq, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Deafness and Other Communication Disorders, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1753290307, Morphogenetic signalling pathways affected in DiGeorge and Charge Syndromes: their role in cardiovascular development. (Renewal), Support for the Rose F. Kennedy IDDRC, Molecular aspects of CRKL in heart development and human disease, The role of HIC2 in cardiovascular morphogenesis, Genetic Modifiers for 22q 11.2 Deletion Syndrome, Developmental mechanisms of human congenital heart disease, Genetic Analysis of Tbx1 in Ear Disorders, 2/2 Brain, Behavior and Genetic Studies of the 22q11 Deletion Studies, 2/5 International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome, G844631639
OpenAlex ID: W2899016780