Chromosome 22, the first human chromosome to be completely sequenced, is prone to genomic alterations. Copy-number variants (CNVs) are common because of an enrichment of low-copy repeat sequences that precipitate a high frequency of nonallelic homologous misalignments and unequal recombination during meiosis. Among these is one of the most common multiple anomaly syndromes in humans and the most common microdeletion syndrome, velocardiofacial syndrome (VCFS), also known as 22q11.2 deletion syndrome and DiGeorge syndrome. This review will focus on the recent literature dealing with both the molecular and clinical aspects of chromosome 22 genomic variations. Although the literature covering this area is expansive, the majority is descriptive or analytical of the problems presented by these genomic disorders, and there is little evidence of translational research including treatment outcomes.
With the increased use of microarray analysis in both research and clinical practice, variations in CNVs are becoming elucidated. Genomic analysis continues to characterize genes and gene effect. Research on the COMT gene continues to yield interesting findings, including a possible sex-mediated effect because of its regulatory role with estrogen. There is a small amount of treatment outcome data relevant to neuropsychiatric disorders in VCFS, but based on small samples and short-term follow-up.
Although hundreds of studies in the past year have focused on genomic disorders of chromosome 22, little progress has been made in the implementation of translational research, even for more common disorders including VCFS.
aDepartment of Laboratory Medicine and Pathology, Seattle Children's Hospital and Department of Laboratory Medicine, University of Washington, Seattle, Washington
bDepartments of Pediatrics and Neurology, Yale University, New Haven, Connecticut
cThe Virtual Center for Velo-Cardio-Facial Syndrome, Manlius, New York, USA
Correspondence to Robert J. Shprintzen, PhD; President, Virtual Center for Velo-Cardio-Facial Syndrome, Inc., Manlius, NY, USA. E-mail: firstname.lastname@example.org