PMID- 17103431
OWN - NLM
STAT- MEDLINE
DCOM- 20070125
LR  - 20200930
IS  - 1552-4825 (Print)
IS  - 1552-4825 (Linking)
VI  - 140
IP  - 24
DP  - 2006 Dec 15
TI  - Detection of low-level mosaicism by array CGH in routine diagnostic specimens.
PG  - 2757-67
AB  - The advent of microarray-based comparative genomic hybridization (array CGH) 
      promises to revolutionize clinical cytogenetics because of its ability to rapidly 
      screen the genome at an unprecedented resolution. Yet, the ability of array CGH 
      to detect and evaluate low-level mosaicism is not known. Our laboratory has 
      analyzed over 3,600 clinical cases with the SignatureChip which we developed for 
      the detection of microdeletions, microduplications, aneuploidy, unbalanced 
      translocations, and subtelomeric and pericentromeric copy number alterations. 
      Here, we report 18 cases of mosaicism detected by array CGH in a routine 
      diagnostic setting, 14 of which were not known to us at the time of the analysis. 
      These 14 cases represent approximately 8% of all abnormal cases identified in our 
      laboratory. For each case, fluorescence in situ hybridization (FISH) analysis was 
      performed on PHA-stimulated cultures after mosaic chromosome abnormalities were 
      suspected by array CGH. In all cases, FISH confirmed the mosaic chromosome 
      abnormalities which included a variety of marker chromosomes, autosomal 
      trisomies, terminal and interstitial deletions, and derivative chromosomes. 
      Interestingly, confirmatory FISH analyses on direct blood smears indicated that 
      the percentage of abnormal cells in unstimulated cultures was in some cases 
      different than that found in PHA-stimulated cells. We also report the detection 
      of a previously unsuspected case of an isochromosome 12p (associated with 
      Pallister-Killian syndrome) by array CGH using genomic DNA extracted from 
      peripheral blood. These results support a growing body of data that suggests that 
      stimulated peripheral blood cultures likely distort the percentage of abnormal 
      cells and may, for some chromosome abnormalities, make their detection unlikely 
      by conventional analysis. Thus, array CGH, which is based on genomic DNA 
      extracted directly from uncultured peripheral blood, may be more likely to detect 
      low-level mosaicism for unbalanced chromosome abnormalities than traditional 
      cytogenetic techniques.
CI  - (c) 2006 Wiley-Liss, Inc.
FAU - Ballif, Blake C
AU  - Ballif BC
AD  - Signature Genomic Laboratories, LLC, Spokane, Washington, USA.
FAU - Rorem, Emily A
AU  - Rorem EA
FAU - Sundin, Kyle
AU  - Sundin K
FAU - Lincicum, Matt
AU  - Lincicum M
FAU - Gaskin, Shannon
AU  - Gaskin S
FAU - Coppinger, Justine
AU  - Coppinger J
FAU - Kashork, Catherine D
AU  - Kashork CD
FAU - Shaffer, Lisa G
AU  - Shaffer LG
FAU - Bejjani, Bassem A
AU  - Bejjani BA
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PL  - United States
TA  - Am J Med Genet A
JT  - American journal of medical genetics. Part A
JID - 101235741
SB  - IM
MH  - Chromosome Aberrations
MH  - Cytogenetic Analysis
MH  - Genetic Testing/*methods
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Mosaicism
MH  - Oligonucleotide Array Sequence Analysis/*methods
EDAT- 2006/11/15 09:00
MHDA- 2007/01/26 09:00
CRDT- 2006/11/15 09:00
PHST- 2006/11/15 09:00 [pubmed]
PHST- 2007/01/26 09:00 [medline]
PHST- 2006/11/15 09:00 [entrez]
AID - 10.1002/ajmg.a.31539 [doi]
PST - ppublish
SO  - Am J Med Genet A. 2006 Dec 15;140(24):2757-67. doi: 10.1002/ajmg.a.31539.