PMID- 17726485
OWN - NLM
STAT- MEDLINE
DCOM- 20080212
LR  - 20071213
IS  - 1018-4813 (Print)
IS  - 1018-4813 (Linking)
VI  - 16
IP  - 1
DP  - 2008 Jan
TI  - Comprehensive analysis of Wolf-Hirschhorn syndrome using array CGH indicates a 
      high prevalence of translocations.
PG  - 45-52
AB  - Wolf-Hirschhorn syndrome (WHS) is caused by deletions involving chromosome region 
      4p16.3. The minimal diagnostic criteria include mild-to-severe mental 
      retardation, hypotonia, growth delay and a distinctive facial appearance. 
      Variable manifestations include feeding difficulties, seizures and major 
      congenital anomalies. Clinical variation may be explained by variation in the 
      size of the deletion. However, in addition to having a deletion involving 4p16.3, 
      previous studies indicate that approximately 15% of WHS patients are also 
      duplicated for another chromosome region due to an unbalanced translocation. It 
      is likely that the prevalence of unbalanced translocations resulting in WHS is 
      underestimated since they can be missed using conventional chromosome analyses 
      such as karyotyping and WHS-specific fluorescence in situ hybridization (FISH). 
      Therefore, we hypothesized that some of the clinical variation may be due to an 
      unrecognized and unbalanced translocation. Array comparative genomic 
      hybridization (aCGH) is a new technology that can analyze the entire genome at a 
      significantly higher resolution over conventional cytogenetics to characterize 
      unbalanced rearrangements. We used aCGH to analyze 33 patients with WHS and found 
      a much higher than expected frequency of unbalanced translocations (15/33, 45%). 
      Seven of these 15 cases were cryptic translocations not detected by a previous 
      karyotype combined with WHS-specific FISH. Three of these 15 cases had an 
      unbalanced translocation involving the short arm of an acrocentric chromosome and 
      were not detected by either aCGH or subtelomere FISH. Analysis of clinical 
      manifestations of each patient also revealed that patients with an unbalanced 
      translocation often presented with exceptions to some expected phenotypes.
FAU - South, Sarah T
AU  - South ST
AD  - Division of Medical Genetics, Department of Pediatrics, University of Utah, Salt 
      Lake City, UT, USA. sarah.south@hsc.utah.edu
FAU - Whitby, Heidi
AU  - Whitby H
FAU - Battaglia, Agatino
AU  - Battaglia A
FAU - Carey, John C
AU  - Carey JC
FAU - Brothman, Arthur R
AU  - Brothman AR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070829
PL  - England
TA  - Eur J Hum Genet
JT  - European journal of human genetics : EJHG
JID - 9302235
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Child, Preschool
MH  - Chromosomes, Human, Pair 4/genetics
MH  - Facies
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Male
MH  - Nucleic Acid Hybridization
MH  - Phenotype
MH  - *Translocation, Genetic
MH  - Wolf-Hirschhorn Syndrome/*genetics/pathology
EDAT- 2007/08/30 09:00
MHDA- 2008/02/13 09:00
CRDT- 2007/08/30 09:00
PHST- 2007/08/30 09:00 [pubmed]
PHST- 2008/02/13 09:00 [medline]
PHST- 2007/08/30 09:00 [entrez]
AID - 5201915 [pii]
AID - 10.1038/sj.ejhg.5201915 [doi]
PST - ppublish
SO  - Eur J Hum Genet. 2008 Jan;16(1):45-52. doi: 10.1038/sj.ejhg.5201915. Epub 2007 
      Aug 29.