A clinical case of inverted duplication with terminal deletion of the short arm of chromosome 5

Cover Page

Cite item

Abstract

The 5p inverted duplication deletion syndrome, also known as inv dup del 5p, is a rare genetic disorder with a prevalence of below 1:1 000 000, whose underlying abnormality lies in a segmental trisomy and simultaneous segmental monosomy of the short arm of chromosome 5. The syndrome was first described by A. Kleczkowska et al. in 1987. According to the literature, large duplications of the chromosome 5 short arm are associated with pronounced phenotypic manifestations, delayed speech and mental development, as well as congenital cardiac, brain and musculoskeletal malformations. We present a description of a clinical case of extended inverted duplication with deletion of the chromosome 5 short arm in a girl with a mild phenotype and no visceral or musculoskeletal abnormalities; we also discuss the pathogenetic mechanisms of chromosomal rearrangement, and conduct a comparative analysis of phenotypic manifestations based on the available literature. Comprehensive molecular cytogenetic assessments have demonstrated that the duplicated site has a length of 29 Mb (5p13.3p15.33), and the deleted site of the subtelomeric region distal to 5p15.33 has a length of 110 kb.

About the authors

O. A. Solovova

Moscow Regional Research and Clinical Institute (MONIKI)

Email: olga_pilyaeva@list.ru
ORCID iD: 0000-0002-1389-4731

Olga А. Solovova – Geneticist, Consultative Department, Center for Medical Genetics

61/2 Shchepkina ul., Moscow, 129110

Russian Federation

N. V. Oparina

Moscow Regional Research and Clinical Institute (MONIKI)

Email: nv_oparina@mail.ru
ORCID iD: 0000-0001-8662-4794

Natalia V. Oparina – Laboratory Geneticist, Medical and Genetical Laboratory, Center for Medical Genetics

61/2 Shchepkina ul., Moscow, 129110

Russian Federation

Yu. Yu. Kotalevskaya

Moscow Regional Research and Clinical Institute (MONIKI)

Author for correspondence.
Email: kotalevskaya@mail.ru
ORCID iD: 0000-0001-8405-8223

Yulia Yu. Kotalevskaya – MD, PhD, Geneticist, Head of the Consultative Department, Center for Medical Genetics

61/2–8 Shchepkina ul., Moscow, 129110

Tel.: +7 (495) 631 72 00

Russian Federation

S. G. Kalinenkova

Moscow Regional Research and Clinical Institute (MONIKI)

Email: s.kalinenkova@monikiweb.ru

Svetlana G. Kalinenkova – MD, PhD, Laboratory Geneticist, Head of Medical and Genetical Laboratory, Center for Medical Genetics

61/2 Shchepkina ul., Moscow, 129110

Russian Federation

A. Sh. Latypov

Moscow Regional Research and Clinical Institute (MONIKI)

Email: a.latypov@monikiweb.ru

Artur Sh. Latypov – MD, PhD, Head of Center for Medical Genetics

61/2 Shchepkina ul., Moscow, 129110

Russian Federation

References

  1. MalaCards Human Disease Database. Chromosome 5p Duplication [Internet]. Available from: https://www.malacards.org/card/chromosome_5p_duplication.
  2. Kleczkowska A, Fryns JP, Moerman P, Vandenberghe K, Van den Berghe H. Trisomy of the short arm of chromosome 5: autopsy data in a malformed newborn with inv dup (5) (p13.1–p15.3). Clin Genet. 1987;32(1):49–56. doi: 10.1111/j.1399-0004.1987.tb03323.x.
  3. Mosca AL, Callier P, Faivre L, Laurent N, Rousseau T, Marle N, Payet M, Guy H, Couvreur S, Masurel-Paulet A, Sagot P, Thauvin-Robinet C, Mugneret F. A prenatal case of inverted duplication with terminal deletion of 5p not including the cat-like cry critical region. Am J Med Genet A. 2011;155A(8):2031–4. doi: 10.1002/ajmg.a.34105.
  4. Izzo A, Genesio R, Ronga V, Nocera V, Marullo L, Cicatiello R, Sglavo G, Paladini D, Conti A, Nitsch L. 40 Mb duplication in chromosome band 5p13.1p15.33 with 800 Kb terminal deletion in a foetus with mild phenotypic features. Eur J Med Genet. 2012;55(2):140–4. doi: 10.1016/j.ejmg.2011.12.004.
  5. Chai H, Grommisch B, DiAdamo A, Wen J, Hui P, Li P. Inverted duplication, triplication and quintuplication through sequential breakage-fusion-bridge events induced by a terminal deletion at 5p in a case of spontaneous abortion. Mol Genet Genomic Med. 2019;7(10):e00965. doi: 10.1002/mgg3.965.
  6. Sreekantaiah C, Kronn D, Marinescu RC, Goldin B, Overhauser J. Characterization of a complex chromosomal rearrangement in a patient with a typical catlike cry and no other clinical findings of cri-du-chat syndrome. Am J Med Genet. 1999;86(3):264–8.
  7. Wang JC, Coe BP, Lomax B, MacLeod PM, Parslow MI, Schein JE, Lam WL, Eydoux P. Inverted duplication with terminal deletion of 5p and no cat-like cry. Am J Med Genet A. 2008;146A(9):1173–9. doi: 10.1002/ajmg.a.32246.
  8. Krgovic D, Blatnik A, Burmas A, Zagorac A, Kokalj Vokac N. A coalescence of two syndromes in a girl with terminal deletion and inverted duplication of chromosome 5. BMC Med Genet. 2014;15:21. doi: 10.1186/1471-2350-15-21.
  9. Vera-Carbonell A, Bafalliu JA, Guillén-Navarro E, Escalona A, Ballesta-Martínez MJ, Fuster C, Fernández A, López-Expósito I. Characterization of a de novo complex chromosomal rearrangement in a patient with cri-du-chat and trisomy 5p syndromes. Am J Med Genet A. 2009;149A(11):2513–21. doi: 10.1002/ajmg.a.33055.
  10. McGowan-Jordan J, Simons A, Schmid M., editors. ISCN 2016: An International System for Human Cytogenomic Nomenclature (2016). 1 st edition. Basel: Karger Publishers; 2016. 140 p.
  11. Database of Genomic Variants. A curated catalogue of human genomic structural variation [Internet]. Available from: http://dgv.tcag.ca/gb2/gbrowse/dgv2_hg19/?name=5p15.33;-search=Search.
  12. ISCA Database Search [Internet]. Available from: http://dbsearch.clinicalgenome.org/search/.
  13. DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) [Internet]. Available from: https://decipher.sanger.ac.uk/search?q=5p13.3#consented-patients/results.
  14. Ballif BC, Yu W, Shaw CA, Kashork CD, Shaffer LG. Monosomy 1p36 breakpoint junctions suggest pre-meiotic breakage-fusion-bridge cycles are involved in generating terminal deletions. Hum Mol Genet. 2003;12(17):2153–65. doi: 10.1093/hmg/ddg231.
  15. Mewar R, Harrison W, Weaver DD, Palmer C, Davee MA, Overhauser J. Molecular cytogenetic determination of a deletion/duplication of 1q that results in a trisomy 18 syndrome-like phenotype. Am J Med Genet. 1994;52(2):178–83. doi: 10.1002/ajmg.1320520211.
  16. De Brasi D, Rossi E, Giglio S, D'Agostino A, Titomanlio L, Farina V, Andria G, Sebastio G. Inv dup del (1)(pter-->q44::q44-->q42:) with the classical phenotype of trisomy 1q42-qter. Am J Med Genet. 2001;104(2):127–30. doi: 10.1002/ajmg.1589.
  17. Bonaglia MC, Giorda R, Poggi G, Raggi ME, Rossi E, Baroncini A, Giglio S, Borgatti R, Zuffardi O. Inverted duplications are recurrent rearrangements always associated with a distal deletion: description of a new case involving 2q. Eur J Hum Genet. 2000;8(8):597–603. doi: 10.1038/sj.ejhg.5200509.
  18. Jenderny J, Poetsch M, Hoeltzenbein M, Friedrich U, Jauch A. Detection of a concomitant distal deletion in an inverted duplication of chromosome 3. Is there an overall mechanism for the origin of such duplications/deficiencies? Eur J Hum Genet. 1998;6(5):439–44. doi: 10.1038/sj.ejhg.5200217.
  19. Kennedy D, Silver MM, Winsor EJ, Toi A, Provias J, Macha M, Precht K, Ledbetter DH, Chitayat D. Inverted duplication of the distal short arm of chromosome 3 associated with lobar holoprosencephaly and lumbosacral meningomyelocele. Am J Med Genet. 2000;91(3):167–70.
  20. Kondoh Y, Toma T, Ohashi H, Harada N, Yoshiura K, Ohta T, Kishino T, Niikawa N, Matsumoto N. Inv dup del(4)(:p14 --> p16.3::p16.3 --> qter) with manifestations of partial duplication 4p and Wolf-Hirschhorn syndrome. Am J Med Genet A. 2003;120A(1):123–6. doi: 10.1002/ajmg.a.20208.
  21. Beaujard MP, Jouannic JM, Bessières B, Borie C, Martin-Luis I, Fallet-Bianco C, Portnoï MF. Prenatal detection of a de novo terminal inverted duplication 4p in a fetus with the Wolf-Hirschhorn syndrome phenotype. Prenat Diagn. 2005;25(6):451–5. doi: 10.1002/pd.1154.
  22. Van Buggenhout G, Maas NM, Fryns JP, Vermeesch JR. A dysmorphic boy with 4qter deletion and 4q32.3-34.3 duplication: clinical, cytogenetic, and molecular findings. Am J Med Genet A. 2004;131(2):186–9. doi: 10.1002/ajmg.a.20679.
  23. Hoo JJ, Chao M, Szego K, Rauer M, Echiverri SC, Harris C. Four new cases of inverted terminal duplication: a modified hypothesis of mechanism of origin. Am J Med Genet. 1995;58(4):299–304. doi: 10.1002/ajmg.1320580402.
  24. Dill FJ, Schertzer M, Sandercock J, Tischler B, Wood S. Inverted tandem duplication generates a duplication deficiency of chromosome 8p. Clin Genet. 1987;32(2):109–13. doi: 10.1111/j.1399-0004.1987.tb03335.x.
  25. Teebi AS, Gibson L, McGrath J, Meyn MS, Breg WR, Yang-Feng TL. Molecular and cytogenetic characterization of 9p-abnormalities. Am J Med Genet. 1993;46(3):288–92. doi: 10.1002/ajmg.1320460310.
  26. Wyandt HE. Reported tandem duplication/deletion of 9q is actually an inverted duplication. Am J Med Genet. 2001;100(1):82–3. doi: 10.1002/ajmg.1172.
  27. Fisher AM, Thomas NS, Cockwell A, Stecko O, Kerr B, Temple IK, Clayton P. Duplications of chromosome 11p15 of maternal origin result in a phenotype that includes growth retardation. Hum Genet. 2002;111(3):290–6. doi: 10.1007/s00439-002-0787-2.
  28. Chen CP, Chern SR, Lin SP, Lin CC, Li YC, Wang TH, Lee CC, Pan CW, Hsieh LJ, Wang W. A paternally derived inverted duplication of distal 14q with a terminal 14q deletion. Am J Med Genet A. 2005;139A(2):146–50. doi: 10.1002/ajmg.a.30997.
  29. Knijnenburg J, van Haeringen A, Hansson KB, Lankester A, Smit MJ, Belfroid RD, Bakker E, Rosenberg C, Tanke HJ, Szuhai K. Ring chromosome formation as a novel escape mechanism in patients with inverted duplication and terminal deletion. Eur J Hum Genet. 2007;15(5):548–55. doi: 10.1038/sj.ejhg.5201807.
  30. Genesio R, De Brasi D, Conti A, Borghese A, Di Micco P, Di Costanzo P, Paladini D, Ungaro P, Nitsch L. Inverted duplication of 15q with terminal deletion in a multiple malformed newborn with intrauterine growth failure and lethal phenotype. Am J Med Genet A. 2004;128A(4):422–8. doi: 10.1002/ajmg.a.30112. Erratum in: Am J Med Genet A. 2005;136(1):113.
  31. Courtens W, Grossman D, Van Roy N, Messiaen L, Vamos E, Toppet V, Haumont D, Streydio C, Jauch A, Vermeesch JR, Speleman F. Noonan-like phenotype in monozygotic twins with a duplication-deficiency of the long arm of chromosome 18 resulting from a maternal paracentric inversion. Hum Genet. 1998;103(4):497–505. doi: 10.1007/s004390050857.
  32. Pangalos C, Théophile D, Sinet PM, Marks A, Stamboulieh-Abazis D, Chettouh Z, Prieur M, Verellen C, Rethoré MO, Lejeune J, et al. No significant effect of monosomy for distal 21q22.3 on the Down syndrome phenotype in "mirror" duplications of chromosome 21. Am J Hum Genet. 1992;51(6):1240–50.
  33. Dupont C, Lebbar A, Teinturier C, Baverel F, Viot G, Le Tessier D, Le Bozec J, Cuisset L, Dupont JM. First reported case of intrachromosomal cryptic inv dup del Xp in a boy with developmental retardation. Am J Med Genet A. 2007;143A(11):1236–43. doi: 10.1002/ajmg.a.31744.
  34. Giglio S, Broman KW, Matsumoto N, Calvari V, Gimelli G, Neumann T, Ohashi H, Voullaire L, Larizza D, Giorda R, Weber JL, Ledbetter DH, Zuffardi O. Olfactory receptor-gene clusters, genomic-inversion polymorphisms, and common chromosome rearrangements. Am J Hum Genet. 2001;68(4):874–83. doi: 10.1086/319506.
  35. Rowe LR, Lee JY, Rector L, Kaminsky EB, Brothman AR, Martin CL, South ST. U-type exchange is the most frequent mechanism for inverted duplication with terminal deletion rearrangements. J Med Genet. 2009;46(10):694–702. doi: 10.1136/jmg.2008.065052.
  36. Weleber RG, Verma RS, Kimberling WJ, Fieger HG Jr, Lubs HA. Duplication-deficiency of the short arm of chromosome 8 following artificial insemination. Ann Genet. 1976;19(4):241–7.
  37. OMIM® Online Mendelian Inheritance in Man®. Cri-du-chat syndrome [Internet]. Available from: https://www.omim.org/entry/123450?-earch=123450&highlight=123450.
  38. Loscalzo ML, Becker TA, Sutcliffe M. A patient with an interstitial duplication of chromosome 5p11–p13.3 further confirming a critical region for 5p duplication syndrome. Eur J Med Genet. 2008;51(1):54–60. doi: 10.1016/j.ejmg.2007.09.006.
  39. Chia NL, Bousfield LR, Johnson BH. A case report of a de novo tandem duplication (5p) (p14----pter). Clin Genet. 1987;31(2):65–9. doi: 10.1111/j.1399-0004.1987.tb02771.x.
  40. Cervera M, Sánchez S, Molina B, Alcántara MA, Del Castillo V, Carnevale A, González-del Angel A. Trisomy of the short arm of chromosome 5 due to a de novo inversion and duplication (5)(p15.3 p13.3). Am J Med Genet A. 2005;136A(4):381–5. doi: 10.1002/ajmg.a.30791.
  41. Avansino JR, Dennis TR, Spallone P, Stock AD, Levin ML. Proximal 5p trisomy resulting from a marker chromosome implicates band 5p13 in 5p trisomy syndrome. Am J Med Genet. 1999;87(1):6–11.
  42. Newman S, Hermetz KE, Weckselblatt B, Rudd MK. Next-generation sequencing of duplication CNVs reveals that most are tandem and some create fusion genes at breakpoints. Am J Hum Genet. 2015;96(2):208–20. doi: 10.1016/j.ajhg.2014.12.017.
  43. Клаг УС, Каммингс МР. Основы генетики. М.: Техносфера; 2007. 896 с.

Supplementary files

There are no supplementary files to display.


Copyright (c) 2020 Solovova O.A., Oparina N.V., Kotalevskaya Y.Y., Kalinenkova S.G., Latypov A.S.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies