PMID- 29636822
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220408
IS  - 1755-8166 (Print)
IS  - 1755-8166 (Electronic)
IS  - 1755-8166 (Linking)
VI  - 11
DP  - 2018
TI  - Maternal interchromosomal insertional translocation leading to 1q43-q44 deletion 
      and duplication in two siblings.
PG  - 24
LID - 10.1186/s13039-018-0371-7 [doi]
LID - 24
AB  - BACKGROUND: 1q43-q44 deletion syndrome is a well-defined chromosomal disorder 
      which is characterized by moderate to severe mental retardation, and variable but 
      characteristic facial features determined by the size of the segment and the 
      number of genes involved. However, patients with 1q43-q44 duplication with a 
      clinical phenotype comparable to that of 1q43-q44 deletion are rarely reported. 
      Moreover, pure 1q43-q44 deletions and duplications derived from balanced 
      insertional translocation within the same family with precisely identified 
      breakpoints have not been reported. CASE PRESENTATION: The proband is a 
      6-year-old girl with profound developmental delay, mental retardation, 
      microcephaly, epilepsy, agenesis of the corpus callosum and hearing impairment. 
      Her younger brother is a 3-month-old boy with macrocephaly and mild developmental 
      delay in gross motor functions. G-banding analysis of the subjects at the 
      400-band level did not reveal any subtle structural changes in their karyotypes. 
      However, single-nucleotide polymorphism (SNP) array analysis showed a deletion 
      and a duplication of approximately 6.0 Mb at 1q43-q44 in the proband and her 
      younger brother, respectively. The Levicare analysis pipeline of whole-genome 
      sequencing (WGS) further demonstrated that a segment of 1q43-q44 was inserted at 
      14q23.1 in the unaffected mother, which indicated that the mother was a carrier 
      of a 46,XX,ins(14;1)(q23.1;q43q44) insertional translocation. Moreover, Sanger 
      sequencing was used to assist the mapping of the breakpoints and the final 
      validation of those breakpoints. The breakpoint on chromosome 1 disrupted the 
      EFCAB2 gene in the first intron, and the breakpoint on chromosome 14 disrupted 
      the PRKCH gene within the 12th intron. In addition, fluorescence in situ 
      hybridization (FISH) further confirmed that the unaffected older sister of the 
      proband carried the same karyotype as the mother. CONCLUSION: Here, we describe a 
      rare family exhibiting pure 1q43-q44 deletion and duplication in two siblings 
      caused by a maternal balanced insertional translocation. Our study demonstrates 
      that WGS with a carefully designed analysis pipeline is a powerful tool for 
      identifying cryptic genomic balanced translocations and mapping the breakpoints 
      at the nucleotide level and could be an effective method for explaining the 
      relationship between karyotype and phenotype.
FAU - Luo, Aixiang
AU  - Luo A
AD  - 1Institute of Reproduction and Stem Cell Engineering, Xiangya School of Medicine, 
      Central South University, Changsha, Hunan 410078 People's Republic of China. 
      ISNI: 0000 0001 0379 7164. GRID: grid.216417.7
FAU - Cheng, Dehua
AU  - Cheng D
AD  - 1Institute of Reproduction and Stem Cell Engineering, Xiangya School of Medicine, 
      Central South University, Changsha, Hunan 410078 People's Republic of China. 
      ISNI: 0000 0001 0379 7164. GRID: grid.216417.7
AD  - 2Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan 410078 
      People's Republic of China. ISNI: 0000 0004 1756 593X. GRID: grid.477823.d
FAU - Yuan, Shimin
AU  - Yuan S
AD  - 2Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan 410078 
      People's Republic of China. ISNI: 0000 0004 1756 593X. GRID: grid.477823.d
FAU - Li, Haiyu
AU  - Li H
AD  - 1Institute of Reproduction and Stem Cell Engineering, Xiangya School of Medicine, 
      Central South University, Changsha, Hunan 410078 People's Republic of China. 
      ISNI: 0000 0001 0379 7164. GRID: grid.216417.7
FAU - Du, Juan
AU  - Du J
AD  - 1Institute of Reproduction and Stem Cell Engineering, Xiangya School of Medicine, 
      Central South University, Changsha, Hunan 410078 People's Republic of China. 
      ISNI: 0000 0001 0379 7164. GRID: grid.216417.7
AD  - 2Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan 410078 
      People's Republic of China. ISNI: 0000 0004 1756 593X. GRID: grid.477823.d
FAU - Zhang, Yang
AU  - Zhang Y
AD  - 3School of Biological Sciences, Faculty of Science, The University of Hong Kong, 
      Hong Kong, 999077 People's Republic of China. ISNI: 0000000121742757. GRID: 
      grid.194645.b
FAU - Yang, Chuanchun
AU  - Yang C
AD  - Cheerland Precision Biomed Co., Ltd., Shenzhen, Guangdong 518055 People's 
      Republic of China.
FAU - Lin, Ge
AU  - Lin G
AD  - 1Institute of Reproduction and Stem Cell Engineering, Xiangya School of Medicine, 
      Central South University, Changsha, Hunan 410078 People's Republic of China. 
      ISNI: 0000 0001 0379 7164. GRID: grid.216417.7
AD  - 2Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan 410078 
      People's Republic of China. ISNI: 0000 0004 1756 593X. GRID: grid.477823.d
FAU - Zhang, Wenyong
AU  - Zhang W
AD  - Southern University of Science and Technology, Shenzhen, Guangdong 518055 
      People's Republic of China.
FAU - Tan, Yue-Qiu
AU  - Tan YQ
AUID- ORCID: 0000-0002-8359-4654
AD  - 1Institute of Reproduction and Stem Cell Engineering, Xiangya School of Medicine, 
      Central South University, Changsha, Hunan 410078 People's Republic of China. 
      ISNI: 0000 0001 0379 7164. GRID: grid.216417.7
AD  - 2Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan 410078 
      People's Republic of China. ISNI: 0000 0004 1756 593X. GRID: grid.477823.d
LA  - eng
PT  - Case Reports
DEP - 20180404
PL  - England
TA  - Mol Cytogenet
JT  - Molecular cytogenetics
JID - 101317942
PMC - PMC5883343
OTO - NOTNLM
OT  - Congenital anomaly
OT  - Insertional translocation
OT  - Pure 1q43-q44 deletion/duplication
OT  - Whole-genome sequencing
COIS- This study was approved by the Institutional Ethics Committee of the Reproductive 
      and Genetic Hospital of Citic-Xiangya, and written informed consent was obtained 
      from all participants prior to genetic analysis.Written informed consent for 
      publication of the images was obtained from the mother of these patients.The 
      authors declare that they have no competing interests.Springer Nature remains 
      neutral with regard to jurisdictional claims in published maps and institutional 
      affiliations.
EDAT- 2018/04/11 06:00
MHDA- 2018/04/11 06:01
PMCR- 2018/04/04
CRDT- 2018/04/12 06:00
PHST- 2018/01/25 00:00 [received]
PHST- 2018/03/08 00:00 [accepted]
PHST- 2018/04/12 06:00 [entrez]
PHST- 2018/04/11 06:00 [pubmed]
PHST- 2018/04/11 06:01 [medline]
PHST- 2018/04/04 00:00 [pmc-release]
AID - 371 [pii]
AID - 10.1186/s13039-018-0371-7 [doi]
PST - epublish
SO  - Mol Cytogenet. 2018 Apr 4;11:24. doi: 10.1186/s13039-018-0371-7. eCollection 
      2018.