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Case Reports
. 2019 Oct 31;12:43.
doi: 10.1186/s13039-019-0455-z. eCollection 2019.

Stable Transmission of Complex Chromosomal Rearrangements Involving Chromosome 1q Derived From Constitutional Chromoanagenesis

Free PMC article
Case Reports

Stable Transmission of Complex Chromosomal Rearrangements Involving Chromosome 1q Derived From Constitutional Chromoanagenesis

Mary A Gudipati et al. Mol Cytogenet. .
Free PMC article


Background: Chromoanagenesis events encompassing chromoanasynthesis, chromoplexy, and chromothripsis are described in cancers and can result in highly complex chromosomal rearrangements derived from 'all-at-once' catastrophic cellular events. The complexity of these rearrangements and the original descriptions in cancer cells initially led to the assumption that it was an acquired anomaly. While rare, these phenomena involving chromosome 1 have been reported a few individuals in a constitutional setting.

Case presentation: Here, we describe a newborn baby who was initially referred for cytogenetic testing for multiple congenital anomalies including cystic encephalomalacia, patent ductus arteriosus, inguinal hernia, and bilateral undescended testicles. Chromosome analysis was performed and revealed a derivative chromosome 1 with an 1q24-q31 segment inserted into 1q42.13 resulting in gain of 1q24-q31. Whole genome SNP microarray analysis showed a complex pattern of copy number variants with four gains and one loss involving 1q24-q31. Mate pair next-generation sequencing analysis revealed 18 chromosome breakpoints, six gains along an 1q24-q31 segment, one deletion of 1q31.3 segment and one deletion of 1q42.13 segment, which is strongly evocative of a chromoanasynthesis event for developing this complex rearrangement. Parental chromosome analyses were performed and showed the same derivative chromosome 1 in the mother.

Conclusions: To our knowledge, our case is the first case with familial constitutional chromoanagenesis involving chromosome 1q24-q42. This report emphasizes the value of performing microarray and mate pair next-generation sequencing analysis for individuals with germline abnormal or complex chromosome rearrangements.

Keywords: Chromoanagenesis; Chromoanasynthesis; Chromoplexy; Chromothripsis; Constitutional 1q abnormalities.

Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.


Fig. 1
Fig. 1
Partial karyogram showing abnormal derivative chromosome 1 from the proband and the mother
Fig. 2
Fig. 2
Copy number changes on the long arm of chromosome 1q24-q31 region. a Genome-wide SNP microarray revealed four gains (blue blocks) and one loss (red block), the X axis is the long arm of chromosome 1q23.3-1q31.3 region, the Y axis is for the copy number, blue and red blocks are for gain and loss of 1q, respectively; b Consistent with Genome-wide SNP microarray, mate pair next-generation sequencing also revealed four gains and one loss. Blue and red lines are for gain and loss of 1q, respectively
Fig. 3
Fig. 3
Characterization of the derivative chromosome 1 by mate pair next-generation sequencing. From left to right: ideogram of chromosome 1, replicating chromosome 1 showing 1q24-q42 region, sister chromatid/homolog chromatid of chromosome 1, and chromosome 1q24–42 had 18 breakpoints, nine chromosome junctions, six gains and two losses, suggesting replication-mediated chromoanasynthesis by fork stalling and template switching or microhomology-mediated break-induced replication as responsible to form a highly complex chromosome 1

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