Complex genomic rearrangements of the Y chromosome in a premature infant.
Chromoanagenesis
Chromothripsis
Complex chromosome rearrangements
Mosaicism
Y chromosome
Journal
Molecular cytogenetics
ISSN: 1755-8166
Titre abrégé: Mol Cytogenet
Pays: England
ID NLM: 101317942
Informations de publication
Date de publication:
26 Aug 2024
26 Aug 2024
Historique:
received:
25
04
2024
accepted:
01
08
2024
medline:
26
8
2024
pubmed:
26
8
2024
entrez:
25
8
2024
Statut:
epublish
Résumé
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. 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. 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.
Sections du résumé
BACKGROUND
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
METHODS
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
CONCLUSIONS
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.
Identifiants
pubmed: 39183314
doi: 10.1186/s13039-024-00689-x
pii: 10.1186/s13039-024-00689-x
doi:
Types de publication
Journal Article
Langues
eng
Pagination
19Informations de copyright
© 2024. The Author(s).
Références
Alkhunaizi E, Albrecht JP, Aarabi M, Witchel SF, Wherrett D, Babul-Hirji R, Dupuis A, Chiniara L, Chater-Diehl E, Shago M, Shuman C, Rajkovic A, Yatsenko SA, Chitayat D. 45,X/46,XY mosaicism: clinical manifestations and long term follow-up. Am J Med Genet: A. 2024;194(3):e63451. https://doi.org/10.1002/ajmg.a.63451 .
doi: 10.1002/ajmg.a.63451
pubmed: 37882230
Bardsley MZ, Kowal K, Levy C, Gosek A, Ayari N, Tartaglia N, Lahlou N, Winder B, Grimes S, Ross JL. 47,XYY syndrome: clinical phenotype and timing of ascertainment. J Pediatr. 2013;163(4):1085–94. https://doi.org/10.1016/j.jpeds.2013.05.037 .
doi: 10.1016/j.jpeds.2013.05.037
pubmed: 23810129
pmcid: 4097881
Berglund A, Viuff MH, Skakkebæk A, Chang S, Stochholm K, Gravholt CH. Changes in the cohort composition of turner syndrome and severe non-diagnosis of Klinefelter, 47,XXX and 47,XYY syndrome: a nationwide cohort study. Orphanet J Rare Dis. 2019;14(1):16. https://doi.org/10.1186/s13023-018-0976-2 .
doi: 10.1186/s13023-018-0976-2
pubmed: 30642344
pmcid: 6332849
Bertelsen B, Nazaryan-Petersen L, Sun W, Mehrjouy MM, Xie G, Chen W, Hjermind LE, Taschner PE, Tümer Z. A germline chromothripsis event stably segregating in 11 individuals through three generations. Genet Medicine: Official J Am Coll Med Genet. 2016;18(5):494–500. https://doi.org/10.1038/gim.2015.112 .
doi: 10.1038/gim.2015.112
Chang HJ, Clark RD, Bachman H. The phenotype of 45,X/46,XY mosaicism: an analysis of 92 prenatally diagnosed cases. Am J Hum Genet. 1990;46(1):156–67.
pubmed: 2294747
pmcid: 1683543
Cools M, Pleskacova J, Stoop H, Hoebeke P, Van Laecke E, Drop SL, Lebl J, Oosterhuis JW, Looijenga LH, Wolffenbuttel KP, Mosaicism Collaborative Group. Gonadal pathology and tumor risk in relation to clinical characteristics in patients with 45,X/46,XY mosaicism. J Clin Endocrinol Metab. 2011;96(7):E1171–80. https://doi.org/10.1210/jc.2011-0232 .
doi: 10.1210/jc.2011-0232
pubmed: 21508138
de Pagter MS, van Roosmalen MJ, Baas AF, Renkens I, Duran KJ, van Binsbergen E, et al. Chromothripsis in healthy individuals affectsmultiple protein-coding genes and can result in severe congenital abnormalities in offspring. Am J Hum Genet. 2015;96(4):651–6. https://doi.org/10.1016/j.ajhg.2015.02.005
Gu H, Jiang JH, Li JY, Zhang YN, Dong XS, Huang YY, Son XM, Lu X, Chen Z. A familial Cri-du-Chat/5p deletion syndrome resulted from rare maternal complex chromosomal rearrangements (CCRs) and/or possible chromosome 5p chromothripsis. PLoS ONE. 2013;8(10):e76985. https://doi.org/10.1371/journal.pone.0076985 .
doi: 10.1371/journal.pone.0076985
pubmed: 24143197
pmcid: 3797133
Kim JW, Park SY, Ryu HM, Lee DE, Lee BY, Kim SY, Park YS, Lee HS, Seo JT. Molecular and clinical characteristics of 26 cases with structural Y chromosome aberrations. Cytogenet Genome Res. 2012;136(4):270–7. https://doi.org/10.1159/000338413 .
doi: 10.1159/000338413
pubmed: 22688216
Kloosterman WP, Guryev V, van Roosmalen M, Duran KJ, de Bruijn E, Bakker SC, Letteboer T, van Nesselrooij B, Hochstenbach R, Poot M, Cuppen E. Chromothripsis as a mechanism driving complex de novo structural rearrangements in the germline. Hum Mol Genet. 2011;20(10):1916–24. https://doi.org/10.1093/hmg/ddr073 .
doi: 10.1093/hmg/ddr073
pubmed: 21349919
Kurtas N, Arrigoni F, Errichiello E, Zucca C, Maghini C, D’Angelo MG, Beri S, Giorda R, Bertuzzo S, Delledonne M, Xumerle L, Rossato M, Zuffardi O, Bonaglia MC. Chromothripsis and ring chromosome 22: a paradigm of genomic complexity in the Phelan-McDermid syndrome (22q13 deletion syndrome). J Med Genet. 2018;55(4):269–77. https://doi.org/10.1136/jmedgenet-2017-105125 .
doi: 10.1136/jmedgenet-2017-105125
pubmed: 29378768
Kurtas NE, Xumerle L, Giussani U, Pansa A, Cardarelli L, Bertini V, Valetto A, Liehr T, Clara Bonaglia M, Errichiello E, Delledonne M, Zuffardi O. Insertional translocation involving an additional nonchromothriptic chromosome in constitutional chromothripsis: rule or exception? Mol Genet Genom Med. 2019;7(2):e00496. https://doi.org/10.1002/mgg3.496 .
doi: 10.1002/mgg3.496
Layman LC, Tho SP, Clark AD, Kulharya A, McDonough PG. Phenotypic spectrum of 45,X/46,XY males with a ring Y chromosome and bilaterally descended testes. Fertil Steril. 2009;91(3):791–7. https://doi.org/10.1016/j.fertnstert.2007.12.078 .
doi: 10.1016/j.fertnstert.2007.12.078
pubmed: 18555994
Liu P, Erez A, Nagamani SC, Dhar SU, Kołodziejska KE, Dharmadhikari AV, Cooper ML, Wiszniewska J, Zhang F, Withers MA, Bacino CA, Campos-Acevedo LD, Delgado MR, Freedenberg D, Garnica A, Grebe TA, Hernández-Almaguer D, Immken L, Lalani SR, McLean SD, Bi W. Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements. Cell. 2011;146(6):889–903. https://doi.org/10.1016/j.cell.2011.07.042 .
doi: 10.1016/j.cell.2011.07.042
pubmed: 21925314
pmcid: 3242451
Lin YW, Hsu LC, Kuo PL, Huang WJ, Chiang HS, Yeh SD, Hsu TY, Yu YH, Hsiao KN, Cantor RM, Yen PH. Partial duplication at AZFc on the Y chromosome is a risk factor for impaired spermatogenesis in Han Chinese in Taiwan. Hum Mutat. 2007;28(5):486–94. https://doi.org/10.1002/humu.20473 .
doi: 10.1002/humu.20473
pubmed: 17285591
Lindhardt Johansen M, Hagen CP, Rajpert-De Meyts E, Kjærgaard S, Petersen BL, Skakkebæk NE, Main KM, Juul A. 45,X/46,XY mosaicism: phenotypic characteristics, growth, and reproductive function–a retrospective longitudinal study. J Clin Endocrinol Metab. 2012;97(8):E1540–9. https://doi.org/10.1210/jc.2012-1388 .
doi: 10.1210/jc.2012-1388
pubmed: 22605431
Mademont-Soler I, Morales C, Madrigal I, Margarit E, Bruguera J, Clusellas N, Martínez JM, Borrell A, Sánchez A, Soler A. Prenatal diagnosis of two different unbalanced forms of an inherited (Y;12) translocation. American journal of medical genetics. Part A. 2009;149A(12):2820–3. https://doi.org/10.1002/ajmg.a.33105 .
doi: 10.1002/ajmg.a.33105
McGinniss MJ, Kazazian HH Jr, Stetten G, Petersen MB, Boman H, Engel E, Greenberg F, Hertz JM, Johnson A, Laca Z. Mechanisms of ring chromosome formation in 11 cases of human ring chromosome 21. Am J Hum Genet. 1992;50(1):15–28.
pubmed: 1346075
pmcid: 1682523
McGowan-Jordan J, Hastings R, Moore S, editors. (2020). ISCN 2020: An International System for Human Cytogenomic Nomenclature (2020). Karger. https://doi.org/10.1159/isbn.978-3-318-06867-2
Pellestor F, Anahory T, Lefort G, Puechberty J, Liehr T, Hédon, B, et al. Complex chromosomal rearrangements: origin and meiotic behavior. Hum Reprod Update. 2011;17(4):476–94. https://doi.org/10.1093/humupd/dmr010
Ravel C, Siffroi JP. Gynecologie obstetrique Fertil. 2009;37(6):511–8. https://doi.org/10.1016/j.gyobfe.2009.04.018 . Anomalies de structure du chromosome Y et syndrome de Turner [Y chromosome structural abnormalities and Turner’s syndrome].
Ross JL, Tartaglia N, Merry DE, Dalva M, Zinn AR. Behavioral phenotypes in males with XYY and possible role of increased NLGN4Y expression in autism features. Genes Brain Behav. 2015;14(2):137–44. https://doi.org/10.1111/gbb.12200 .
doi: 10.1111/gbb.12200
pubmed: 25558953
Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, Smith MJ, Foster JW, Frischauf AM, Lovell-Badge R, Goodfellow PN. A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature. 1990;346(6281):240–4. https://doi.org/10.1038/346240a0 .
doi: 10.1038/346240a0
pubmed: 1695712
Stephens, P. J., Greenman, C. D., Fu, B., Yang, F., Bignell, G. R., Mudie, L. J., Pleasance, E. D., Lau, K. W., Beare, D., Stebbings, L. A., McLaren, S., Lin, M. L., McBride, D. J., Varela, I., Nik-Zainal, S., Leroy, C., Jia, M., Menzies, A., Butler, A. P., Teague, J. W., … Campbell, P. J. (2011). Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell, 144(1), 27–40. https://doi.org/10.1016/j.cell.2010.11.055.
Stetten G, Tuck-Muller CM, Blakemore KJ, Wong C, Kazazian HH Jr, Antonarakis SE. Evidence for involvement of a robertsonian translocation 13 chromosome in formation of a ring chromosome 13. Mol Biol Med. 1990;7(6):479–84.
pubmed: 2077349
Telvi L, Lebbar A, Del Pino O, Barbet JP, Chaussain JL. 45,X/46,XY mosaicism: report of 27 cases. Pediatrics. 1999;104(2 Pt 1):304–8. https://doi.org/10.1542/peds.104.2.304 .
doi: 10.1542/peds.104.2.304
pubmed: 10429013
Willis MJ, Bird LM, Dell’aquilla M, Jones MC. (2006). Natural history of prenatally diagnosed 46,X,isodicentric Y. Prenatal diagnosis, 26(2), 134–137. https://doi.org/10.1002/pd.1352
Zhao Y, Gardner EJ, Tuke MA, Zhang H, Pietzner M, Koprulu M, Jia RY, Ruth KS, Wood AR, Beaumont RN, Tyrrell J, Jones SE, Allen L, Day H, Langenberg FR, Frayling C, Weedon TM, Perry MN, Ong JRB, K. K., Murray A. Detection and characterization of male sex chromosome abnormalities in the UK Biobank study. Genet Medicine: Official J Am Coll Med Genet. 2022;24(9):1909–19. https://doi.org/10.1016/j.gim.2022.05.011 .
doi: 10.1016/j.gim.2022.05.011
Zhou R, Cheng J, Ma D, Tan J, Wang Y, Hu P, Xu Z. Identifying Novel Copy Number variants in Azoospermia factor regions and evaluating their effects on Spermatogenic Impairment. Front Genet. 2019;10:427. https://doi.org/10.3389/fgene.2019.00427 .
doi: 10.3389/fgene.2019.00427
pubmed: 31134133
pmcid: 6514098