Duplication of Yq- and proximal Yp-arms with deletion of almost all PAR1 (including SHOX) in a young man with non-obstructive azoospermia, short stature and skeletal defects

Abstract

Duplications of Yq arm (and AZF) seems to be tolerated by fertile males, while mutations, deletions, duplications or haploinsufficiency of SHOX can originate a wide range of phenotypes, including short stature and skeletal abnormalities. We report a case of non-obstructive azoospermia in a young man with short stature, skeletal anomalies, normal intelligence and hormonal parameters. This male showed a very singular Y-chromosome aberration, consisting of a duplication of Yq and proximal regions of Yp, with a deletion of almost all PAR1 in Yptel, including SHOX. CBA- and RBA-banding and FISH-mapping with telomeric, centromeric, AZF and SHOX probes were used. These results were confirmed by array CGH, which revealed the following karyotype constitution: arr [hg19] Xp22.33 or Yp11.32p11.31 (310,932–2,646,815 or 260,932–2,596,815) ×1, Yp11.2q12 (8,641,183–59,335,913) ×2. We conclude that the haploinsufficience of SHOX may be the cause of short stature and skeletal defects in the patient, while the non-obstructive azoospermia could be related to the lack of X–Y pairing during meiosis originated by the anomalous configuration of this chromosome abnormality and large deletion which occurred in Yp-PAR1.

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References

  1. Bardsley MZ, Kowal K, Levy C, Gosek A, Ayari N, Tartaglia N, Lahlou N, Winder B, Grimes S, Ross JL (2013) 47,XYY syndrome: clinical phenotype and timing of ascertainment. J Pediatr 163(4):1085–1094

    Article  PubMed  PubMed Central  Google Scholar 

  2. Bergamo P, Volpe MG, Lorenzetti S, Mantovani A, Notari T, Cocca E, Cerullo S, Di Stasio M, Cerino P, Montano L (2016) Human semen as an early, sensitive biomarker of highly polluted living environment in healthy men: a pilot biomonitoring study on trace elements in blood and semen and their relationship with sperm quality and RedOx status. Reprod Toxicol 66:1–9

    CAS  Article  PubMed  Google Scholar 

  3. Berger R (1975) The incidence of constitutional chromosome aberrations. J Genet Hum 23:42–49

    PubMed  Google Scholar 

  4. Bispo AV, Burégio-Frota P, Oliveira dos Santos L, Leal GF, Duarte AR, Araújo J, Cavalcante da Silva V, Muniz MT, Liehr T, Santos N (2014) Y chromosome in Turner syndrome: detection of hidden mosaicism and the report of a rare X;Y translocation case. Reprod Fertil Dev 26(8):1176–1182

    CAS  Article  PubMed  Google Scholar 

  5. Bojesen A, Juul S, Gravholt CH (2003) Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J Clin Endocrinol Metab 88:622–626

    CAS  Article  PubMed  Google Scholar 

  6. Dobek WA, Kim HG, Walls CA, Chorich LP, Tho SP, Wang ZX, McDonough PG, Layman LC (2015) Long-term follow-up of females with unbalanced X;Y translocations-reproductive and nonreproductive consequences. Mol Cytogenet 8:13

    Article  PubMed  PubMed Central  Google Scholar 

  7. Gatta V, Palka C, Chiavaroli V, Franchi S, Cannataro G, Savastano M, Cotroneo AR, Chiarelli F, Mohn A, Stuppia L (2014) Spectrum of phenotypic anomalies in four families with deletion of the SHOX enhancer region. BMC Med Genet 15:87

    Article  PubMed  PubMed Central  Google Scholar 

  8. Geerts M, Steyaert J, Fryns JP (2003) The XYY syndrome: a follow-up study on 38 boys. Genet Couns 14:267–279

    CAS  PubMed  Google Scholar 

  9. Guilherme RS, Klein E, Hamid AB, Bhatt S, Volleth M, Polityko A, Kulpanovich A, Dufke A, Albrecht B, Morlot S, Brecevic L, Petersen MB, Manolakos E, Kosyakova N, Liehr T (2013) Human ring chromosomes—new insights for their clinical significance. Balkan J Med Genet 16(1):13–20

    PubMed  PubMed Central  Google Scholar 

  10. Gunel M, Cavkaytar S, Ceylaner G, Batioglu S (2008) Azoospermia and cryptorchidism in a male with a de novo reciprocal t(Y;16) translocation. Genet Couns 19(3):277–280

    CAS  PubMed  Google Scholar 

  11. Hemmat M, Hemmat O, Boyar FZ (2013) Isochromosome Yp and jumping translocation of Yq resulting in five cell lines in an infertile male: a case report and review of the literature. Mol Cytogenet 6:36

    Article  PubMed  PubMed Central  Google Scholar 

  12. Hofherr SE, Wiktor AE, Kipp BR, Dawson DB, Van Dyke DL (2011) Clinical diagnostic testing for the cytogenetic and molecular causes of male infertility: the Mayo Clinic experience. J Assist Reprod Genet 28:1091–1098

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hsu H-K, Su M-T, Chen M, Yen P, Kuo P-L (2014) Two Y chromosomes with duplication of the distal long arm including the entire AZFc region. Gene 536:444–448

    CAS  Article  PubMed  Google Scholar 

  14. Hunter H, Quaife R (1973) A 48,XYYY male: a somatic and psychiatric description. J Med Genet Mar 10(1):80–83

    CAS  Article  Google Scholar 

  15. Iannuzzi L, Di Berardino D (2008) Tools of the trade: diagnostics and research in domestic animal cytogenetics. J Appl Genet 49(4):357–366

    Article  PubMed  Google Scholar 

  16. Jo WH, Jung MK, Kim KE, Chae HW, Kim DH, Kwon AR, Kim H-S (2015) XYY syndrome: a 13-year-old boy with tall stature. Ann Pediatr Endocrinol Metab 20:170–173

    Article  PubMed  PubMed Central  Google Scholar 

  17. Margari L, Lamanna AL, Craig F, Simone M, Gentile M (2014) Autism spectrum disorders in XYY syndrome: two new cases and systematic review of the literature. Eur J Pediatr 173:277–283

    Article  PubMed  Google Scholar 

  18. Shi Q, Martin RH (2000) Aneuploidy in human sperm: a review of the frequency and distribution of aneuploidy, effects of donor age and lifestyle factors. Cytogenet Cell Genet 90:219–226

    CAS  Article  PubMed  Google Scholar 

  19. Valetto A, Bertini V, Michelucci A, Toschi B, Dati E, Baroncelli GI, Bertelloni S (2016) Short stature in isodicentric Y chromosome and three copies of the SHOX gene: clinical report and review of literature. Mol Syndromol 7:19–25

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. Vinasco Sandoval GT, Jaimes GC, Coll Barrios M, Cespedes C, Velasco HM (2014) SHOX gene and conserved noncoding element deletions/duplications in Colombian patients with idiopathic short stature. Mol Genet Genomic Med 2(2):95–102

    Article  Google Scholar 

  21. Wiland E, Yatsenko AN, Kishore A, Stanczak H, Zdarta A, Ligaj M, Olszewska M, Wolski JK, Kurpisz M (2015) FISH and array CGH characterization of de novo derivative Y chromosome (Yq duplication and partial Yp deletion) in an azoospermic male. Reprod Biomed Online 31(2):217–224

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The study has been partially supported by the “EcoFoodFertility” project. The authors wish to thank Mr. Domenico Incarnato, CNR-ISPAAM of Naples for his excellent technical assistance.

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Authors

Contributions

DC performed array CGH and GTG-banding karyotypes and contributed to the data interpretation; AI and AP performed CBA- and RBA-banding karyotypes, all FISH-mapping analyses and contributed to the data interpretation; LM recruited the subject and performed the sperm analysis; OC provided the BAC clones; CS acquired some data and contributed to the data interpretation; MLV performed hormonal analyses, skeletal X-graph and contributed to the data interpretation; MU revised critically the manuscript for important intellectual content; LI and VV conceived the study and wrote the paper. All authors revised the manuscript and approved the final version.

Corresponding author

Correspondence to Leopoldo Iannuzzi.

Ethics declarations

We have the informed consent from the patient for this publication.

Conflict of interest

None.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. In particular, all studies conducted under the EcoFoodFertility project have been approved by the Ethical Committee, Coordination Service of the ASL Napoli 3, Naples, Italy, as reported in the Directive Determination N. 56 of July 15, 2015.

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Communicated by: Michal Witt

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Cancemi, D., Iannuzzi, A., Perucatti, A. et al. Duplication of Yq- and proximal Yp-arms with deletion of almost all PAR1 (including SHOX) in a young man with non-obstructive azoospermia, short stature and skeletal defects. J Appl Genetics 58, 481–486 (2017). https://doi.org/10.1007/s13353-017-0412-7

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Keywords

  • Y-chromosome aberration
  • Yq duplication
  • PAR1 deletion
  • Male infertility
  • Azoospermia
  • Short stature
  • Skeletal anomalies