PMID- 26543751
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20151106
LR  - 20200930
IS  - 2193-1801 (Print)
IS  - 2193-1801 (Electronic)
IS  - 2193-1801 (Linking)
VI  - 4
DP  - 2015
TI  - 5p13.3p13.2 duplication associated with developmental delay, congenital 
      malformations and chromosome instability manifested as low-level aneuploidy.
PG  - 616
LID - 10.1186/s40064-015-1399-3 [doi]
LID - 616
AB  - Recent developments in molecular cytogenetics allow the detection of genomic 
      rearrangements at an unprecedented level leading to discoveries of previously 
      unknown chromosomal imbalances (zygotic and post-zygotic/mosaic). These can be 
      accompanied by a different kind of pathological genome variations, i.e. 
      chromosome instability (CIN) manifested as structural chromosomal rearrangements 
      and low-level mosaic aneuploidy. Fortunately, combining whole-genome and 
      single-cell molecular cytogenetic techniques with bioinformatics offers an 
      opportunity to link genomic changes to specific molecular or cellular pathology. 
      High-resolution chromosomal SNP microarray analysis was performed to study the 
      genome of a 15-month-aged boy presented with developmental delay, congenital 
      malformations, feeding problems, deafness, epileptiform activity, and eye 
      pathology. In addition, somatic chromosomal mutations (CIN) were analyzed by 
      fluorescence in situ hybridization (FISH). Interstitial 5p13.3p13.2 duplication 
      was revealed in the index patient. Moreover, CIN manifested almost exclusively as 
      chromosome losses and gains (aneuploidy) was detected. Using bioinformatic 
      analysis of SNP array data and FISH results, CIN association with the genomic 
      imbalance resulted from the duplication was proposed. The duplication was 
      demonstrated to encompass genes implicated in cell cycle, programmed cell death, 
      chromosome segregation and genome stability maintenance pathways as shown by an 
      interactomic analysis. Genotype-phenotype correlations were observed, as well. To 
      the best our knowledge, identical duplications have not been reported in the 
      available literature. Apart from genotype-phenotype correlations, it was possible 
      to propose a link between the duplication and CIN (aneuploidy). This case study 
      demonstrates that combining SNP array genomic analysis, bioinformatics and 
      molecular cytogenetic evaluation of somatic genome variations is able to provide 
      a view on cellular and molecular pathology in a personalized manner. Therefore, 
      one can speculate that similar approaches targeting both interindividual and 
      intercellular genomic variations could be useful for a better understanding of 
      disease mechanisms and disease-related biological processes.
FAU - Iourov, Ivan Y
AU  - Iourov IY
AD  - Mental Health Research Center, Russian Academy of Medical Sciences, Moscow, 
      117152 Russia ; Russian National Research Medical University named after N.I. 
      Pirogov, Separated Structural Unit "Clinical Research Institute of Pediatrics", 
      Ministry of Health of Russian Federation, Moscow, 125412 Russia ; Department of 
      Medical Genetics, Russian Medical Academy of Postgraduate Education, Moscow, 
      123995 Russia.
FAU - Vorsanova, Svetlana G
AU  - Vorsanova SG
AD  - Mental Health Research Center, Russian Academy of Medical Sciences, Moscow, 
      117152 Russia ; Russian National Research Medical University named after N.I. 
      Pirogov, Separated Structural Unit "Clinical Research Institute of Pediatrics", 
      Ministry of Health of Russian Federation, Moscow, 125412 Russia.
FAU - Demidova, Irina A
AU  - Demidova IA
AD  - Mental Health Research Center, Russian Academy of Medical Sciences, Moscow, 
      117152 Russia ; Russian National Research Medical University named after N.I. 
      Pirogov, Separated Structural Unit "Clinical Research Institute of Pediatrics", 
      Ministry of Health of Russian Federation, Moscow, 125412 Russia.
FAU - Aliamovskaia, Galina A
AU  - Aliamovskaia GA
AD  - Russian National Research Medical University named after N.I. Pirogov, Separated 
      Structural Unit "Clinical Research Institute of Pediatrics", Ministry of Health 
      of Russian Federation, Moscow, 125412 Russia.
FAU - Keshishian, Elena S
AU  - Keshishian ES
AD  - Russian National Research Medical University named after N.I. Pirogov, Separated 
      Structural Unit "Clinical Research Institute of Pediatrics", Ministry of Health 
      of Russian Federation, Moscow, 125412 Russia.
FAU - Yurov, Yuri B
AU  - Yurov YB
AD  - Mental Health Research Center, Russian Academy of Medical Sciences, Moscow, 
      117152 Russia ; Russian National Research Medical University named after N.I. 
      Pirogov, Separated Structural Unit "Clinical Research Institute of Pediatrics", 
      Ministry of Health of Russian Federation, Moscow, 125412 Russia.
LA  - eng
PT  - Journal Article
DEP - 20151015
PL  - Switzerland
TA  - Springerplus
JT  - SpringerPlus
JID - 101597967
PMC - PMC4628017
OTO - NOTNLM
OT  - 5p13 duplication
OT  - Aneuploidy
OT  - Bioinformatics
OT  - Chromosome instability
OT  - Mosaicism
EDAT- 2015/11/07 06:00
MHDA- 2015/11/07 06:01
PMCR- 2015/10/15
CRDT- 2015/11/07 06:00
PHST- 2015/05/13 00:00 [received]
PHST- 2015/10/05 00:00 [accepted]
PHST- 2015/11/07 06:00 [entrez]
PHST- 2015/11/07 06:00 [pubmed]
PHST- 2015/11/07 06:01 [medline]
PHST- 2015/10/15 00:00 [pmc-release]
AID - 1399 [pii]
AID - 10.1186/s40064-015-1399-3 [doi]
PST - epublish
SO  - Springerplus. 2015 Oct 15;4:616. doi: 10.1186/s40064-015-1399-3. eCollection 
      2015.