The recurrent distal 22q11.2 microdeletions are often de novo and do not represent a single clinical entity: a proposed categorization system

The five segmental duplications (LCR22-D to -H) at the distal region of chromosome 22 band q11.2 in the region immediately distal to the DiGeorge/velocardiofacial syndrome deleted region have been implicated in the recurrent distal 22q11.2 microdeletions. To date, the distal 22q11.2 microdeletions h...

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Bibliographic Details
Published in:Genetics in medicine 2014-01, Vol.16 (1), p.92-100
Main Authors: Mikhail, Fady M, Burnside, Rachel D, Rush, Brooke, Ibrahim, Jennifer, Godshalk, Robin, Rutledge, S Lane, Robin, Nathaniel H, Descartes, Maria D, Carroll, Andrew J
Format: Article
Language:English
Subjects:
Abnormalities, Multiple - diagnosis
Abnormalities, Multiple - genetics
Abnormalities, Multiple - pathology
Adolescent
Child
Child, Preschool
Chromosome Deletion
Chromosomes, Human, Pair 22 - genetics
Comparative Genomic Hybridization
DiGeorge Syndrome - diagnosis
DiGeorge Syndrome - genetics
DiGeorge Syndrome - pathology
Female
Genetic Variation
Humans
Male
Phenotype
Polymorphism, Single Nucleotide
Young Adult
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Summary:The five segmental duplications (LCR22-D to -H) at the distal region of chromosome 22 band q11.2 in the region immediately distal to the DiGeorge/velocardiofacial syndrome deleted region have been implicated in the recurrent distal 22q11.2 microdeletions. To date, the distal 22q11.2 microdeletions have been grouped together as a single clinical entity despite the fact that these deletions are variable in size and position depending on the mediating LCR22s. Here, we report 13 new unrelated patients with variable size deletions in the distal 22q11.2 region as shown by cytogenomic array analyses. We compare our patients' clinical features with those of previously reported cases to better dissect the phenotypic correlations based on the deletion size and position. Six patients had the 1.1-Mb deletion flanked by LCR22-D and -E, and presented clinically with a phenotype consistent with previously reported cases with distal 22q11.2 microdeletions. Three patients had the 1.8-Mb deletion flanked by LCR22-D and -F, and presented with a similar phenotype. Four patients had the 700-kb deletion flanked by LCR22-E and -F, and presented with a milder phenotype that lacked growth restriction and cardiovascular defects. We suggest that the recurrent distal 22q11.2 microdeletions do not represent a single clinical entity, and propose categorizing these deletions into three types according to their genomic position. All three deletion types are thought to be pathogenic and are most often de novo. They all share some presenting features but also have their unique features and risks.
ISSN:1098-3600
1530-0366
DOI:10.1038/gim.2013.79