Journal of Assisted Reproduction and Genetics

, Volume 36, Issue 12, pp 2533–2539 | Cite as

Analysis of molecular cytogenetic features and PGT-SR for two infertile patients with small supernumerary marker chromosomes

  • Dehua Cheng
  • Shimin Yuan
  • Duo Yi
  • Keli Luo
  • Fang Xu
  • Fei Gong
  • Changfu Lu
  • Guangxiu Lu
  • Ge Lin
  • Yue-Qiu TanEmail author


Research question

Can preimplantation genetic testing for structural rearrangement (PGT-SR) with next-generation sequencing (NGS) be used to infertile patients carrying small supernumerary marker chromosomes (sSMCs)?


In this study, two infertile patients carrying ring sSMCs were recruited. Different molecular cytogenetic techniques were performed to identify the features of the two sSMCs, followed by clinical PGT-SR cycles.


The results of G-banding and FISH showed that patient 1’s sSMC originated from the 8p23-p10 region, with a resulting karyotype of [ 47,XY, del(8)(p23p10), +r(8)(p23p10).ish del(8)(CEP8+,subtle 8p+,subtle 8q+),r(8)(CEP8+,subtle 8p-,subtle 8q-)[55/60].arr(1-22) ×2,(X,Y)×1]. The sSMC of patient 2 was derived from chromosome 3 and further microdissection with next-generation sequencing (MicroSeq) revealed it contained the region of chromosome 3 between 93,504,855 and 103,839,892 bp (GRCh37), which involved 52 known genes. So the karyotype of patient 2 was 47,XX, +mar.ish der(3)(CEP3+,subtle 3p-,subtle 3q-)[49/60].arr[GRCh37] 3q11.2q13.1(93,500,001_103,839,892) ×3(0.5). PGT-SR with NGS was performed to provide reproductive guidance for the two patients. For patient 1, four balanced euploid embryos and four embryos with partial trisomy/monosomy of (8p23.1-8p11.21) were obtained, and a balanced euploid embryo was successfully implanted and had resulted in a healthy baby. For patient 2, an embryo with monosomy of sex chromosomes and another embryo with a duplication at (3q11-q13.1), neither of which was available for implantation.


The identification of the origins and structural characteristics of rare sSMCs should rely on different molecular cytogenetic techniques. PGT-SR is an alternative fertility treatment for these patients carrying sSMCs. This study may provide directions for the assisted reproductive therapy for infertile patients with sSMC.


Small supernumerary marker chromosome (sSMC) Chromosome microdissection Next-generation sequencing Preimplantation genetic testing 


Funding information

The authors are grateful to the patients and their family members for participating in this study. This study was supported by a grant from the National Natural Science Foundation of China (No. 81471432), the Science and Technology Major Project of the Ministry of Science and Technology of Hunan Province, China (No. 2017SK1030), and National Key Research & Developmental Program of China (No. 2018YFC1004900).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


  1. 1.
    Al-Rikabi ABH, Pekova S, Fan X, Jancuskova T, Liehr T. Small supernumerary marker chromosome may provide information on dosage-insensitive pericentric regions in human. Curr Genomics. 2018;19:192–9.CrossRefGoogle Scholar
  2. 2.
    Alfarawati S, Fragouli E, Colls P, Wells D. First births after preimplantation genetic diagnosis of structural chromosome abnormalities using comparative genomic hybridization and microarray analysis. Hum Reprod. 2011;26:1560–74.CrossRefGoogle Scholar
  3. 3.
    Armanet N, Tosca L, Brisset S, Liehr T, Tachdjian G. Small supernumerary marker chromosomes in human infertility. Cytogenet Genome Res. 2015;146:100–8.CrossRefGoogle Scholar
  4. 4.
    Batanian JR, Huang Y, Gottesman GS, Grange DK, Blasingame AV. Preferential involvement of the short arm in chromosome 8-derived supernumerary markers and ring as identified by chromosome arm painting. Am J Med Genet. 2000;90:276–82.CrossRefGoogle Scholar
  5. 5.
    Cheng DH, Gong F, Tan K, Lu CF, Lin G, Lu GX, et al. Karyotype determination and reproductive guidance for short stature women with a hidden Y chromosome fragment. Reprod BioMed Online. 2013;27:89–95.CrossRefGoogle Scholar
  6. 6.
    Crolla JA, Youings SA, Ennis S, Jacobs PA. Supernumerary marker chromosomes in man: parental origin, mosaicism and maternal age revisited. Eur J Hum Genet. 2005;13:154–60.CrossRefGoogle Scholar
  7. 7.
    Hochstenbach R, van Gijn ME, Krijtenburg PJ, Raemakers R, van’t Slot R, Renkens I, et al. Mol Syndromol. 2013;3:274–83.CrossRefGoogle Scholar
  8. 8.
    Hu L, Cheng D, Gong F, Lu C, Tan Y, Luo K, et al. Reciprocal translocation carrier diagnosis in preimplantation human embryos. EBioMedicine. 2016;14:139–47.CrossRefGoogle Scholar
  9. 9.
    Kogan JM, Miller E, Ware SM. High resolution SNP based microarray mapping of mosaic supernumerary marker chromosomes 13 and 17: delineating novel loci for apraxia. Am J Med Genet A. 2009;149A:887–93.CrossRefGoogle Scholar
  10. 10.
    Liehr T, Claussen U, Starke H. Small supernumerary marker chromosomes (sSMC) in humans. Cytogenet Genome Res. 2004;107:55–67.CrossRefGoogle Scholar
  11. 11.
    Liehr T, Mrasek K, Weise A, Dufke A, Rodriguez L, Martinez GN, et al. Small supernumerary marker chromosomes--progress towards a genotype-phenotype correlation. Cytogenet Genome Res. 2006;112:23–34.CrossRefGoogle Scholar
  12. 12.
    Liehr T, Weise A. Frequency of small supernumerary marker chromosomes in prenatal, newborn, developmentally retarded and infertility diagnostics. Int J Mol Med. 2007;19:719–31.PubMedGoogle Scholar
  13. 13.
    Manvelyan M, Riegel M, Santos M, Fuster C, Pellestor F, Mazaurik ML, et al. Thirty-two new cases with small supernumerary marker chromosomes detected in connection with fertility problems: detailed molecular cytogenetic characterization and review of the literature. Int J MolMed. 2008;21:705–14.Google Scholar
  14. 14.
    Murthy SK, Malhotra AK, Jacob PS, Naveed S, Al-Rowaished EE, Mani S, et al. Analphoid supernumerary marker chromosome characterized by aCGH and FISH as inv dup(3)(q25.33qter) de novo in a child with dysmorphic features and streaky pigmentation: case report. Mol Cytogenet. 2008;1:19.CrossRefGoogle Scholar
  15. 15.
    Olszewska M, Wanowska E, Kishore A, Huleyuk N, Georgiadis AP, Yatsenko AN, et al. Genetic dosage and position effect of small supernumerary marker chromosome (sSMC) in human sperm nuclei in infertile male patient. Sci Rep. 2015;5:17408.CrossRefGoogle Scholar
  16. 16.
    Ou J, Wang W, Liehr T, Klein E, Hamid AB, Wang F, et al. Characterization of three small supernumerary marker chromosomes (sSMC) in humans. J Matern Fetal Neonatal Med. 2013;26:106–8.CrossRefGoogle Scholar
  17. 17.
    Scriven PN, Handyside AH, Ogilvie CM. Chromosome translocations: segregation modes and strategies for preimplantation genetic diagnosis. Prenat Diagn. 1998;18:1437–49.CrossRefGoogle Scholar
  18. 18.
    Starke H, Nietzel A, Weise A, Heller A, Mrasek K, Belitz B, et al. Small supernumerary marker chromosomes (SMCs): genotype-phenotype correlation and classification. Hum Genet. 2003;114:51–67.CrossRefGoogle Scholar
  19. 19.
    Tan Y, Yin X, Zhang S, Jiang H, Tan K, Li J, et al. Clinical outcome of preimplantation genetic diagnosis and screening using next generation sequencing. Gigascience. 2014;3:30.CrossRefGoogle Scholar
  20. 20.
    Viersbach R, Engels H, Gamerdinger U, Hansmann M. Delineation of supernumerary marker chromosomes in 38 patients. Am J Med Genet. 1998;76:351–8.CrossRefGoogle Scholar
  21. 21.
    Watson MS, Dowton SB, Rohrbaugh J. Case of direct insertion within a chromosome 3 leading to a chromosome 3p duplication in an offspring. Am J Med Genet. 1990;36:172–4.CrossRefGoogle Scholar
  22. 22.
    Yu S, Fiedler SD, Brawner SJ, Joyce JM, Zhou XG, Liu HY. Characterizing small supernumerary marker chromosomes with combination of multiple techniques. Cytogenet Genome Res. 2012;136:6–14.CrossRefGoogle Scholar
  23. 23.
    Schmid M, McGowan-Jordan J, Simons A. An International system for human cytogenomic nomenclature (ISCN 2016). Reprint of: Cytogenetic and Genome Research. 2016;149:1–2.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute of Reproduction and Stem Cell Engineering, School of Basic Medical ScienceCentral South UniversityChangshaChina
  2. 2.Reproductive and Genetic Hospital of CITIC-XiangyaChangshaChina
  3. 3.Key Laboratory of Human Stem Cell and Reproductive EngineeringMinistry of HealthChangshaChina
  4. 4.National Engineering and Research Center of Human Stem CellsChangshaChina

Personalised recommendations