A germline chromothripsis event stably segregating in 11 individuals through three generations
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
A germline chromothripsis event stably segregating in 11 individuals through three generations. / Bertelsen, Birgitte; Nazaryan-Petersen, Lusine; Sun, Wei; Mehrjouy, Mana M; Xie, Gangcai; Chen, Wei; Hjermind, Lena E; Taschner, Peter E M; Tümer, Zeynep.
I: Genetics In Medicine, Bind 18, Nr. 5, 2016, s. 494-500.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - A germline chromothripsis event stably segregating in 11 individuals through three generations
AU - Bertelsen, Birgitte
AU - Nazaryan-Petersen, Lusine
AU - Sun, Wei
AU - Mehrjouy, Mana M
AU - Xie, Gangcai
AU - Chen, Wei
AU - Hjermind, Lena E
AU - Taschner, Peter E M
AU - Tümer, Zeynep
PY - 2016
Y1 - 2016
N2 - PURPOSE: Parentally transmitted germ-line chromothripsis (G-CTH) has been identified in only a few cases. Most of these rearrangements were stably transmitted, in an unbalanced form, from a healthy mother to her child with congenital abnormalities probably caused by de novo copy-number changes of dosage sensitive genes. We describe a G-CTH transmitted through three generations in 11 healthy carriers.METHODS: Conventional cytogenetic analysis, mate-pair sequencing, and polymerase chain reaction (PCR) were used to identify the chromosome rearrangement and characterize the breakpoints in all three generations.RESULTS: We identified an apparently balanced translocation t(3;5), later shown to be a G-CTH, in all individuals of a three-generation family. The G-CTH stably segregated without occurrence of additional rearrangements; however, several spontaneous abortions were reported, possibly due to unbalanced transmission. Although seven protein-coding genes are interrupted, no clinical features can be definitively attributed to the affected genes. However, it can be speculated that truncation of one of these genes, encoding ataxia-telangiectasia and Rad3-related protein kinase (ATR), a key component of the DNA damage response, may be related to G-CTH formation.CONCLUSION: G-CTH rearrangements are not always associated with abnormal phenotypes and may be misinterpreted as balanced two-way translocations, suggesting that G-CTH is an underdiagnosed phenomenon.Genet Med 18 5, 494-500.
AB - PURPOSE: Parentally transmitted germ-line chromothripsis (G-CTH) has been identified in only a few cases. Most of these rearrangements were stably transmitted, in an unbalanced form, from a healthy mother to her child with congenital abnormalities probably caused by de novo copy-number changes of dosage sensitive genes. We describe a G-CTH transmitted through three generations in 11 healthy carriers.METHODS: Conventional cytogenetic analysis, mate-pair sequencing, and polymerase chain reaction (PCR) were used to identify the chromosome rearrangement and characterize the breakpoints in all three generations.RESULTS: We identified an apparently balanced translocation t(3;5), later shown to be a G-CTH, in all individuals of a three-generation family. The G-CTH stably segregated without occurrence of additional rearrangements; however, several spontaneous abortions were reported, possibly due to unbalanced transmission. Although seven protein-coding genes are interrupted, no clinical features can be definitively attributed to the affected genes. However, it can be speculated that truncation of one of these genes, encoding ataxia-telangiectasia and Rad3-related protein kinase (ATR), a key component of the DNA damage response, may be related to G-CTH formation.CONCLUSION: G-CTH rearrangements are not always associated with abnormal phenotypes and may be misinterpreted as balanced two-way translocations, suggesting that G-CTH is an underdiagnosed phenomenon.Genet Med 18 5, 494-500.
U2 - 10.1038/gim.2015.112
DO - 10.1038/gim.2015.112
M3 - Journal article
C2 - 26312826
VL - 18
SP - 494
EP - 500
JO - Genetics in Medicine
JF - Genetics in Medicine
SN - 1098-3600
IS - 5
ER -
ID: 161736060