PMID- 32355308
OWN - NLM
STAT- MEDLINE
DCOM- 20210208
LR  - 20210420
IS  - 1435-232X (Electronic)
IS  - 1434-5161 (Linking)
VI  - 65
IP  - 9
DP  - 2020 Sep
TI  - Analyses of breakpoint junctions of complex genomic rearrangements comprising 
      multiple consecutive microdeletions by nanopore sequencing.
PG  - 735-741
LID - 10.1038/s10038-020-0762-6 [doi]
AB  - The widespread use of genomic copy number analysis has revealed many previously 
      unknown genomic structural variations, including some which are more complex. In 
      this study, three consecutive microdeletions were identified in the same 
      chromosome by microarray-based comparative genomic hybridization (aCGH) analysis 
      for a patient with a neurodevelopmental disorder. Subsequent fluorescence in situ 
      hybridization (FISH) analyses unexpectedly suggested complicated translocations 
      and inversions. For better understanding of the mechanism, breakpoint junctions 
      were analyzed by nanopore sequencing, as a new long-read whole-genome sequencing 
      (WGS) tool. The results revealed a new chromosomal disruption, giving rise to 
      four junctions in chromosome 7. According the sequencing results of breakpoint 
      junctions, all junctions were considered as the consequence of multiple 
      double-strand breaks and the reassembly of DNA fragments by nonhomologous 
      end-joining, indicating chromothripsis. KMT2E, located within the deletion 
      region, was considered as the gene responsible for the clinical features of the 
      patient. Combinatory usage of aCGH and FISH analyses would be recommended for 
      interpretation of structural variations analyzed through WGS.
FAU - Imaizumi, Taichi
AU  - Imaizumi T
AD  - Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
AD  - Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, 
      Japan.
FAU - Yamamoto-Shimojima, Keiko
AU  - Yamamoto-Shimojima K
AD  - Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
AD  - Tokyo Women's Medical University Institute for Integrated Medical Sciences, 
      Tokyo, Japan.
FAU - Yanagishita, Tomoe
AU  - Yanagishita T
AD  - Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan.
FAU - Ondo, Yumiko
AU  - Ondo Y
AD  - Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
FAU - Yamamoto, Toshiyuki
AU  - Yamamoto T
AUID- ORCID: 0000-0002-9484-3505
AD  - Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan. 
      yamamoto.toshiyuki@twmu.ac.jp.
AD  - Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, 
      Japan. yamamoto.toshiyuki@twmu.ac.jp.
AD  - Tokyo Women's Medical University Institute for Integrated Medical Sciences, 
      Tokyo, Japan. yamamoto.toshiyuki@twmu.ac.jp.
AD  - Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan. 
      yamamoto.toshiyuki@twmu.ac.jp.
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20200430
PL  - England
TA  - J Hum Genet
JT  - Journal of human genetics
JID - 9808008
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (KMT2E protein, human)
SB  - IM
MH  - *Chromosome Aberrations
MH  - Chromosome Breakage
MH  - Chromosome Inversion
MH  - Comparative Genomic Hybridization/*methods
MH  - DNA Breaks, Double-Stranded
MH  - DNA Copy Number Variations
MH  - DNA End-Joining Repair
MH  - DNA-Binding Proteins/*genetics
MH  - Female
MH  - Genetic Association Studies
MH  - Genome, Human
MH  - Genomics/*methods
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Nanopore Sequencing
MH  - Neurodevelopmental Disorders/*genetics
MH  - Oligonucleotide Array Sequence Analysis
MH  - Sequence Inversion
MH  - Translocation, Genetic
MH  - Whole Genome Sequencing
MH  - Young Adult
EDAT- 2020/05/02 06:00
MHDA- 2021/02/09 06:00
CRDT- 2020/05/02 06:00
PHST- 2019/09/08 00:00 [received]
PHST- 2020/04/04 00:00 [accepted]
PHST- 2020/04/01 00:00 [revised]
PHST- 2020/05/02 06:00 [pubmed]
PHST- 2021/02/09 06:00 [medline]
PHST- 2020/05/02 06:00 [entrez]
AID - 10.1038/s10038-020-0762-6 [pii]
AID - 10.1038/s10038-020-0762-6 [doi]
PST - ppublish
SO  - J Hum Genet. 2020 Sep;65(9):735-741. doi: 10.1038/s10038-020-0762-6. Epub 2020 
      Apr 30.