PMID- 16170807
OWN - NLM
STAT- MEDLINE
DCOM- 20060613
LR  - 20191210
IS  - 1098-1004 (Electronic)
IS  - 1059-7794 (Linking)
VI  - 26
IP  - 5
DP  - 2005 Nov
TI  - Detection of cryptic subtelomeric chromosome abnormalities and identification of 
      anonymous chromatin using a quantitative multiplex ligation-dependent probe 
      amplification (MLPA) assay.
PG  - 477-86
AB  - The need to detect clinically significant segmental aneuploidies beyond the range 
      of light microscopy demands the development of new cost-efficient, sensitive, and 
      robust analytical techniques. Multiplex ligation-dependent probe amplification 
      (MLPA) has already been shown to be particularly effective and flexible for 
      measuring copy numbers in a multiplex format. Previous attempts to develop a 
      reliable MLPA to assay all chromosome subtelomeric regions have been confounded 
      by unforeseen copy number variation in some genes that are very close to the 
      telomeres in healthy individuals. We addressed this shortcoming by substituting 
      all known polymorphic probes and using two complementary multiplex assays to 
      minimize the likelihood of false results. We developed this new quantitative MLPA 
      strategy for two important diagnostic applications. First, in a group of cases 
      with high clinical suspicion of a chromosome abnormality but normal, 
      high-resolution karyotypes, MLPA detected subtelomeric abnormalities in three 
      patients. Two were de novo terminal deletions (del(4p) and del(1p)), and one was 
      a derivative chromosome 1 from a maternal t(1p;17p). The range of these segmental 
      aneuploidies was 1.8-6.6 Mb, and none were visible on retrospective microscopy. 
      Second, in a group of six patients with apparently de novo single-chromosome 
      abnormalities containing anonymous chromatin, MLPA identified two cases with 
      simple intrachromosomal duplications: dup(6p) and dup(8q). Three cases showed 
      derivative chromosomes from translocations involving the distal regions of 9q and 
      4q, 5p and 11q, and 6q and 3p. One case showed a nonreciprocal, interchromosomal 
      translocation of the distal region of 10p-7p. All abnormalities in both groups 
      were confirmed by fluorescence in situ hybridization (FISH) using bacterial 
      artificial chromosomes (BACs). This quantitative MLPA technique for subtelomeric 
      assays is compared with previously described alternative techniques.
CI  - Copyright 2005 Wiley-Liss, Inc.
FAU - Northrop, Emma L
AU  - Northrop EL
AD  - Genetic Health Services Victoria and Murdoch Children's Research Institute, 
      Department of Paediatrics, University of Melbourne, Royal Children's Hospital, 
      Parkville, Australia.
FAU - Ren, Hua
AU  - Ren H
FAU - Bruno, Damien L
AU  - Bruno DL
FAU - McGhie, James D R
AU  - McGhie JD
FAU - Coffa, Jordi
AU  - Coffa J
FAU - Schouten, Jan
AU  - Schouten J
FAU - Choo, K H Andy
AU  - Choo KH
FAU - Slater, Howard R
AU  - Slater HR
LA  - eng
PT  - Comparative Study
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (Chromatin)
SB  - IM
MH  - Adolescent
MH  - Aneuploidy
MH  - Child
MH  - Child, Preschool
MH  - Chromatin
MH  - *Chromosome Aberrations
MH  - Cytogenetic Analysis/*methods
MH  - Developmental Disabilities/diagnosis/genetics
MH  - Female
MH  - Humans
MH  - Intellectual Disability/diagnosis/genetics
MH  - Male
MH  - *Nucleic Acid Amplification Techniques
MH  - Telomere
MH  - Translocation, Genetic
EDAT- 2005/09/20 09:00
MHDA- 2006/06/14 09:00
CRDT- 2005/09/20 09:00
PHST- 2005/09/20 09:00 [pubmed]
PHST- 2006/06/14 09:00 [medline]
PHST- 2005/09/20 09:00 [entrez]
AID - 10.1002/humu.20243 [doi]
PST - ppublish
SO  - Hum Mutat. 2005 Nov;26(5):477-86. doi: 10.1002/humu.20243.