PMID- 18179902
OWN - NLM
STAT- MEDLINE
DCOM- 20080130
LR  - 20220317
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 82
IP  - 1
DP  - 2008 Jan
TI  - 22q11.2 distal deletion: a recurrent genomic disorder distinct from DiGeorge 
      syndrome and velocardiofacial syndrome.
PG  - 214-21
LID - 10.1016/j.ajhg.2007.09.014 [doi]
AB  - Microdeletions within chromosome 22q11.2 cause a variable phenotype, including 
      DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS). About 97% of 
      patients with DGS/VCFS have either a common recurrent approximately 3 Mb deletion 
      or a smaller, less common, approximately 1.5 Mb nested deletion. Both deletions 
      apparently occur as a result of homologous recombination between nonallelic 
      flanking low-copy repeat (LCR) sequences located in 22q11.2. Interestingly, 
      although eight different LCRs are located in proximal 22q, only a few cases of 
      atypical deletions utilizing alternative LCRs have been described. Using 
      array-based comparative genomic hybridization (CGH) analysis, we have detected 
      six unrelated cases of deletions that are within 22q11.2 and are located distal 
      to the approximately 3 Mb common deletion region. Further analyses revealed that 
      the rearrangements had clustered breakpoints and either a approximately 1.4 Mb or 
      approximately 2.1 Mb recurrent deletion flanked proximally by LCR22-4 and 
      distally by either LCR22-5 or LCR22-6, respectively. Parental fluorescence in 
      situ hybridization (FISH) analyses revealed that none of the available parents 
      (11 out of 12 were available) had the deletion, indicating de novo events. All 
      patients presented with characteristic facial dysmorphic features. A history of 
      prematurity, prenatal and postnatal growth delay, developmental delay, and mild 
      skeletal abnormalities was prevalent among the patients. Two patients were found 
      to have a cardiovascular malformation, one had truncus arteriosus, and another 
      had a bicuspid aortic valve. A single patient had a cleft palate. We conclude 
      that distal deletions of chromosome 22q11.2 between LCR22-4 and LCR22-6, although 
      they share some characteristic features with DGS/VCFS, represent a novel genomic 
      disorder distinct genomically and clinically from the well-known DGS/VCF deletion 
      syndromes.
FAU - Ben-Shachar, Shay
AU  - Ben-Shachar S
AD  - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 
      TX 77030, USA.
FAU - Ou, Zhishuo
AU  - Ou Z
FAU - Shaw, Chad A
AU  - Shaw CA
FAU - Belmont, John W
AU  - Belmont JW
FAU - Patel, Millan S
AU  - Patel MS
FAU - Hummel, Marybeth
AU  - Hummel M
FAU - Amato, Stephen
AU  - Amato S
FAU - Tartaglia, Nicole
AU  - Tartaglia N
FAU - Berg, Jonathan
AU  - Berg J
FAU - Sutton, V Reid
AU  - Sutton VR
FAU - Lalani, Seema R
AU  - Lalani SR
FAU - Chinault, A Craig
AU  - Chinault AC
FAU - Cheung, Sau W
AU  - Cheung SW
FAU - Lupski, James R
AU  - Lupski JR
FAU - Patel, Ankita
AU  - Patel A
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
SB  - IM
MH  - Abnormalities, Multiple/*genetics
MH  - *Chromosome Deletion
MH  - *Chromosomes, Human, Pair 22
MH  - DiGeorge Syndrome/*genetics
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Syndrome
PMC - PMC2253964
EDAT- 2008/01/09 09:00
MHDA- 2008/01/31 09:00
PMCR- 2008/07/10
CRDT- 2008/01/09 09:00
PHST- 2007/07/16 00:00 [received]
PHST- 2007/09/04 00:00 [revised]
PHST- 2007/09/12 00:00 [accepted]
PHST- 2008/01/09 09:00 [pubmed]
PHST- 2008/01/31 09:00 [medline]
PHST- 2008/01/09 09:00 [entrez]
PHST- 2008/07/10 00:00 [pmc-release]
AID - S0002-9297(07)00020-1 [pii]
AID - AJHG19 [pii]
AID - 10.1016/j.ajhg.2007.09.014 [doi]
PST - ppublish
SO  - Am J Hum Genet. 2008 Jan;82(1):214-21. doi: 10.1016/j.ajhg.2007.09.014.