PMID- 18033723
OWN - NLM
STAT- MEDLINE
DCOM- 20080402
LR  - 20211020
IS  - 1098-1004 (Electronic)
IS  - 1059-7794 (Print)
IS  - 1059-7794 (Linking)
VI  - 29
IP  - 3
DP  - 2008 Mar
TI  - Detailed analysis of 22q11.2 with a high density MLPA probe set.
PG  - 433-40
AB  - The presence of chromosome-specific low-copy repeats (LCRs) predisposes 
      chromosome 22 to deletions and duplications. The current diagnostic procedure for 
      detecting aberrations at 22q11.2 is chromosomal analysis coupled with 
      fluorescence in situ hybridization (FISH) or PCR-based multiplex ligation 
      dependent probe amplification (MLPA). However, there are copy number variations 
      (CNVs) in 22q11.2 that are only detected by high-resolution platforms such as 
      array comparative genomic hybridization (aCGH). We report on development of a 
      high-definition MLPA (MLPA-HD) 22q11 kit that detects copy number changes at 37 
      loci on the long arm of chromosome 22. These include the 3-Mb region commonly 
      deleted in DiGeorge/velocardiofacial syndrome (DGS/VCFS), the cat eye syndrome 
      (CES) region, and more distal regions in 22q11 that have recently been shown to 
      be deleted. We have used this MLPA-HD probe set to analyze 363 previously 
      well-characterized samples with a variety of different rearrangements at 22q11 
      and demonstrate that it can detect copy number alterations with high sensitivity 
      and specificity. In addition to detection of the common recurrent deletions 
      associated with DGS/VCFS, variant and novel chromosome 22 aberrations have been 
      detected. These include duplications within as well as deletions distal to this 
      region. Further, the MLPA-HD detects deletion endpoint differences between 
      patients with the common 3-Mb deletion. The MLPA-HD kit is proposed as a cost 
      effective alternative to the currently available detection methods for 
      individuals with features of the 22q11 aberrations. In patients with the relevant 
      phenotypic characteristics, this MLPA-HD probe set could replace FISH for the 
      clinical diagnosis of 22q11.2 deletions and duplications.
FAU - Jalali, G R
AU  - Jalali GR
AD  - Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, 
      Pennsylvania 19104-4318, USA.
FAU - Vorstman, J A S
AU  - Vorstman JA
FAU - Errami, Ab
AU  - Errami A
FAU - Vijzelaar, R
AU  - Vijzelaar R
FAU - Biegel, J
AU  - Biegel J
FAU - Shaikh, T
AU  - Shaikh T
FAU - Emanuel, B S
AU  - Emanuel BS
LA  - eng
GR  - CA 39926/CA/NCI NIH HHS/United States
GR  - R01 HL084410/HL/NHLBI NIH HHS/United States
GR  - R01 HL084410-02/HL/NHLBI NIH HHS/United States
GR  - R01 CA039926-20/CA/NCI NIH HHS/United States
GR  - P50 HL074731/HL/NHLBI NIH HHS/United States
GR  - HL 74731/HL/NHLBI NIH HHS/United States
GR  - R01 CA039926/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
SB  - IM
MH  - Chromosome Aberrations
MH  - Chromosome Deletion
MH  - Chromosomes, Human, Pair 22/*genetics
MH  - Coloboma/genetics
MH  - Craniofacial Abnormalities/genetics
MH  - DiGeorge Syndrome/genetics
MH  - Gene Dosage
MH  - Genetic Variation
MH  - Humans
MH  - *Molecular Probe Techniques
MH  - Nucleic Acid Amplification Techniques/methods
MH  - Rhabdoid Tumor/genetics
PMC - PMC2664158
MID - NIHMS91801
EDAT- 2007/11/23 09:00
MHDA- 2008/04/03 09:00
PMCR- 2009/04/01
CRDT- 2007/11/23 09:00
PHST- 2007/11/23 09:00 [pubmed]
PHST- 2008/04/03 09:00 [medline]
PHST- 2007/11/23 09:00 [entrez]
PHST- 2009/04/01 00:00 [pmc-release]
AID - 10.1002/humu.20640 [doi]
PST - ppublish
SO  - Hum Mutat. 2008 Mar;29(3):433-40. doi: 10.1002/humu.20640.