PMID- 35248119
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220318
IS  - 1755-8166 (Print)
IS  - 1755-8166 (Electronic)
IS  - 1755-8166 (Linking)
VI  - 15
IP  - 1
DP  - 2022 Mar 5
TI  - Characterization of a rare mosaic unbalanced translocation of t(3;12) in a 
      patient with neurodevelopmental disorders.
PG  - 10
LID - 10.1186/s13039-022-00579-0 [doi]
LID - 10
AB  - BACKGROUND: Unbalanced translocations may be de novo or inherited from one parent 
      carrying the balanced form and are usually present in all cells. Mosaic 
      unbalanced translocations are extremely rare with a highly variable phenotype 
      depending on the tissue distribution and level of mosaicism. Mosaicism for 
      structural chromosomal abnormalities is clinically challenging for diagnosis and 
      counseling due to the limitation of technical platforms and complex mechanisms, 
      respectively. Here we report a case with a tremendously rare maternally-derived 
      mosaic unbalanced translocation of t(3;12), and we illustrate the unreported 
      complicated mechanism using single nucleotide polymorphism (SNP) array, 
      fluorescence in situ hybridization (FISH), and chromosome analyses. CASE 
      PRESENTATION: An 18-year-old female with a history of microcephaly, pervasive 
      developmental disorder, intellectual disability, sensory integration disorder, 
      gastroparesis, and hypotonia presented to our genetics clinic. She had negative 
      karyotype by parental report but no other genetic testing performed previously. 
      SNP microarray analysis revealed a complex genotype including 8.4 Mb terminal 
      mosaic duplication on chromosome 3 (3p26.3->3p26.1) with the distal 5.7 Mb 
      involving two parental haplotypes and the proximal 2.7 Mb involving three 
      parental haplotypes, and a 6.1 Mb terminal mosaic deletion on chromosome 12 
      (12p13.33->12p13.31) with no evidence for a second haplotype. Adjacent to the 
      mosaic deletion is an interstitial mosaic copy-neutral region of homozygosity 
      (1.9 Mb, 12p13.31). The mother of this individual was confirmed by chromosome 
      analysis and FISH that she carries a balanced translocation, 
      t(3;12)(p26.1;p13.31). CONCLUSION: Taken together, the proband, when at the stage 
      of a zygote, likely carried the derivative chromosome 12 from this translocation, 
      and a postzygotic mitotic recombination event occurred between the normal 
      paternal chromosome 12 and maternal derivative chromosome 12 to "correct" the 
      partial 3p trisomy and partial deletion of 12p. To the best of our knowledge, it 
      is the first time to report the mechanism utilizing a combined cytogenetic and 
      cytogenomic approach, and we believe it expands our knowledge of mosaic 
      structural chromosomal disorders and provides new insight into clinical 
      management and genetic counseling.
CI  - (c) 2022. The Author(s).
FAU - Hu, Xiaolin
AU  - Hu X
AUID- ORCID: 0000-0002-4893-9944
AD  - Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH, USA.
FAU - Baker, Elizabeth K
AU  - Baker EK
AUID- ORCID: 0000-0002-4709-5700
AD  - Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH, USA.
AD  - Department of Pediatrics, University of Cincinnati College of Medicine, 3333 
      Burnet Ave, Cincinnati, OH, USA.
FAU - Johnson, Jodie
AU  - Johnson J
AD  - Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH, USA.
FAU - Balow, Stephanie
AU  - Balow S
AD  - Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH, USA.
AD  - Department of Pediatrics, University of Cincinnati College of Medicine, 3333 
      Burnet Ave, Cincinnati, OH, USA.
FAU - Pena, Loren D M
AU  - Pena LDM
AD  - Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH, USA.
AD  - Department of Pediatrics, University of Cincinnati College of Medicine, 3333 
      Burnet Ave, Cincinnati, OH, USA.
FAU - Conlin, Laura K
AU  - Conlin LK
AD  - Division of Genomic Diagnostics, Children's Hospital of Philadelphia, 
      Philadelphia, PA, USA.
FAU - Guan, Qiaoning
AU  - Guan Q
AD  - Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH, USA.
AD  - Department of Pediatrics, University of Cincinnati College of Medicine, 3333 
      Burnet Ave, Cincinnati, OH, USA.
FAU - Smolarek, Teresa A
AU  - Smolarek TA
AD  - Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH, USA. teresa.smolarek@cchmc.org.
AD  - Department of Pediatrics, University of Cincinnati College of Medicine, 3333 
      Burnet Ave, Cincinnati, OH, USA. teresa.smolarek@cchmc.org.
LA  - eng
PT  - Journal Article
DEP - 20220305
PL  - England
TA  - Mol Cytogenet
JT  - Molecular cytogenetics
JID - 101317942
PMC - PMC8898488
OTO - NOTNLM
OT  - Mitotic rescue
OT  - SNP microarray
OT  - Unbalanced translocation
COIS- There are no relevant conflicts of interest to disclose.
EDAT- 2022/03/07 06:00
MHDA- 2022/03/07 06:01
PMCR- 2022/03/05
CRDT- 2022/03/06 20:25
PHST- 2021/10/19 00:00 [received]
PHST- 2022/01/28 00:00 [accepted]
PHST- 2022/03/06 20:25 [entrez]
PHST- 2022/03/07 06:00 [pubmed]
PHST- 2022/03/07 06:01 [medline]
PHST- 2022/03/05 00:00 [pmc-release]
AID - 10.1186/s13039-022-00579-0 [pii]
AID - 579 [pii]
AID - 10.1186/s13039-022-00579-0 [doi]
PST - epublish
SO  - Mol Cytogenet. 2022 Mar 5;15(1):10. doi: 10.1186/s13039-022-00579-0.