PMID- 29721507
OWN - NLM
STAT- MEDLINE
DCOM- 20180918
LR  - 20231112
IS  - 2314-6141 (Electronic)
IS  - 2314-6133 (Print)
VI  - 2018
DP  - 2018
TI  - Cytogenomic Integrative Network Analysis of the Critical Region Associated with 
      Wolf-Hirschhorn Syndrome.
PG  - 5436187
LID - 10.1155/2018/5436187 [doi]
LID - 5436187
AB  - Deletions in the 4p16.3 region are associated with Wolf-Hirschhorn syndrome 
      (WHS), a contiguous gene deletion syndrome involving variable size deletions. In 
      this study, we perform a cytogenomic integrative analysis combining classical 
      cytogenetic methods, fluorescence in situ hybridization (FISH), chromosomal 
      microarray analysis (CMA), and systems biology strategies, to establish the 
      cytogenomic profile involving the 4p16.3 critical region and suggest WHS-related 
      intracellular cell signaling cascades. The cytogenetic and clinical patient 
      profiles were evaluated. We characterized 12 terminal deletions, one interstitial 
      deletion, two ring chromosomes, and one classical translocation 4;8. CMA allowed 
      delineation of the deletions, which ranged from 3.7 to 25.6 Mb with breakpoints 
      from 4p16.3 to 4p15.33. Furthermore, the smallest region of overlapping (SRO) 
      encompassed seven genes in a terminal region of 330 kb in the 4p16.3 region, 
      suggesting a region of susceptibility to convulsions and microcephaly. Therefore, 
      molecular interaction networks and topological analysis were performed to 
      understand these WHS-related symptoms. Our results suggest that specific cell 
      signaling pathways including dopamine receptor, NAD+ nucleosidase activity, and 
      fibroblast growth factor-activated receptor activity are associated with the 
      diverse pathological WHS phenotypes and their symptoms. Additionally, we 
      identified 29 hub-bottlenecks (H-B) nodes with a major role in WHS.
FAU - Correa, Thiago
AU  - Correa T
AD  - Post-Graduate Program in Genetics and Molecular Biology, Universidade Federal do 
      Rio Grande do Sul (UFRGS), 91501-970 Porto Alegre, RS, Brazil.
FAU - Mergener, Rafaella
AU  - Mergener R
AD  - Post-Graduate Program in Genetics and Molecular Biology, Universidade Federal do 
      Rio Grande do Sul (UFRGS), 91501-970 Porto Alegre, RS, Brazil.
FAU - Leite, Julio Cesar Loguercio
AU  - Leite JCL
AD  - Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Rua Ramiro 
      Barcelos 2350, 90035-903 Porto Alegre, RS, Brazil.
FAU - Galera, Marcial Francis
AU  - Galera MF
AD  - Department of Pediatrics, Universidade Federal do Mato Grosso (UFMT), 78600-000 
      Cuiaba, MT, Brazil.
FAU - Moreira, Lilia Maria de Azevedo
AU  - Moreira LMA
AD  - Post-Graduate Program in Genetics and Biodiversity, Universidade Federal da 
      Bahia, Campus Ondina, 40170-290 Salvador, BA, Brazil.
FAU - Vargas, Jose Eduardo
AU  - Vargas JE
AUID- ORCID: 0000-0002-7729-5738
AD  - Institute of Biological Sciences, Universidade de Passo Fundo, Passo Fundo, RS, 
      Brazil.
FAU - Riegel, Mariluce
AU  - Riegel M
AUID- ORCID: 0000-0002-6397-1301
AD  - Post-Graduate Program in Genetics and Molecular Biology, Universidade Federal do 
      Rio Grande do Sul (UFRGS), 91501-970 Porto Alegre, RS, Brazil.
AD  - Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Rua Ramiro 
      Barcelos 2350, 90035-903 Porto Alegre, RS, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20180312
PL  - United States
TA  - Biomed Res Int
JT  - BioMed research international
JID - 101600173
SB  - IM
MH  - *Chromosome Deletion
MH  - *Chromosome Painting
MH  - Chromosomes, Human, Pair 4/*genetics
MH  - Female
MH  - *Gene Regulatory Networks
MH  - Humans
MH  - Male
MH  - Retrospective Studies
MH  - Wolf-Hirschhorn Syndrome/*genetics
PMC - PMC5867687
EDAT- 2018/05/04 06:00
MHDA- 2018/09/19 06:00
PMCR- 2018/03/12
CRDT- 2018/05/04 06:00
PHST- 2017/10/06 00:00 [received]
PHST- 2018/02/01 00:00 [accepted]
PHST- 2018/05/04 06:00 [entrez]
PHST- 2018/05/04 06:00 [pubmed]
PHST- 2018/09/19 06:00 [medline]
PHST- 2018/03/12 00:00 [pmc-release]
AID - 10.1155/2018/5436187 [doi]
PST - epublish
SO  - Biomed Res Int. 2018 Mar 12;2018:5436187. doi: 10.1155/2018/5436187. eCollection 
      2018.