Complex genomic rearrangements of the Y chromosome in a premature infant

Mol Cytogenet. 2024 Aug 26;17(1):19. doi: 10.1186/s13039-024-00689-x.

Abstract

Background: Chromoanagenesis is an umbrella term used to describe catastrophic "all at once" cellular events leading to the chaotic reconstruction of chromosomes. It is characterized by numerous rearrangements involving a small number of chromosomes/loci, copy number gains in combination with deletions, reconstruction of chromosomal fragments with improper order/orientation, and preserved heterozygosity in copy number neutral regions. Chromoanagesis is frequently described in association with cancer; however, it has also been described in the germline. The clinical features associated with constitutional chromoanagenesis are typically due to copy number changes and/or disruption of genes or regulatory regions.

Case presentation: We present an 8-year-old male patient with complex rearrangements of the Y chromosome including a ring Y chromosome, a derivative Y;21 chromosome, and a complex rearranged Y chromosome. These chromosomes were characterized by G-banded chromosome analysis, SNP microarray, interphase FISH, and metaphase FISH. The mechanism(s) by which these rearrangements occurred is unclear; however, it is evocative of chromoanagenesis.

Conclusion: This case is a novel example of suspected germline chromoanagenesis leading to large copy number changes that are well-tolerated, possibly because only the sex chromosomes are affected.

Keywords: Chromoanagenesis; Chromothripsis; Complex chromosome rearrangements; Mosaicism; Y chromosome.