Duplications in 19p13.3 are associated with male infertility



To identify genomic imbalances and candidate loci in idiopathic male infertility.


Affymetrix CytoScan 750K Array was used to analyze genomic imbalances and candidate loci in 34 idiopathic infertile cases of different phenotypes (hypo-spermatogenesis, n = 8; maturation arrest, n = 7; and Sertoli cell-only syndrome, n = 13, severe oligozoospermia, n = 6, and 10 normozoospermic fertile men). Ten ethnically matched controls were screened for comparison.


The cytogenetic array analysis detected a genomic gain at the 19p13.3 region in 9 (26.47%) cases, with the highest frequency in patients with Sertoli cell-only syndrome (SCOS) (38%). Its complete absence in the control group suggests its likely pathogenic nature. In addition to Y-classical, micro, and partial deletions, the duplication in 19p13.3 could serve as a unique biomarker for evaluation of infertility risk. The common region across the individuals harboring the duplication identified STK11, ATP5D, MIDN, CIRBP, and EFNA2 genes which make them strong candidates for further investigations. The largest duplicated region identified in this study displayed a major network of 7 genes, viz., CIRBP, FSTL3, GPX4, GAMT, KISS1R, STK11, and PCSK4, associated with reproductive system development and function. The role of chance was ruled out by screening of ethnically matched controls.


The result clearly indicates the significance of 19p13.3 duplication in infertile men with severe testicular phenotypes. The present study underlines the utility and significance of whole genomic analysis in the cases of male infertility which goes undiagnosed due to limitations in the conventional cytogenetic techniques and for identifying genes that are essential for spermatogenesis.

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The authors thank the patients for providing blood samples and their consent for genetic analysis. We would like to acknowledge the Interdisciplinary School of Life Sciences (ISLS), Banaras Hindu University for Affymetrix Microarray Facility. The first author thanks CSIR for the Senior Research Fellowship.


The study was funded by the Board of Research in Nuclear Sciences (BRNS), Govt. of India, with sanction number 2013/37B/27/BRNS.

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Corresponding author

Correspondence to Kiran Singh.

Ethics declarations

This study was approved by the Institutional Human Ethics Committee of the Institute of Science, Banaras Hindu University, Varanasi, approved this study (Approval letter No. Dean/2011-12/119).

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Informed consent was obtained from all individual participants included in the study.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee.

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The authors declare that they have no competing interests.

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a Microarray results for 19p13.3 duplication using CytoScan™ 750K Array (Affymetrix, USA). Analysis using the ChAS software (Affymetrix, USA) showed a common genomic gain at the 19p13.3 region in 9 (26.47%) cases (P1 to P9). The locus and extent of duplication in all the nine cases are represented by bold blue lines. For comparison, one control (CONTROL2) is used which shows an absence of duplication. b Representative microarray profile of patient with the largest 19p13.3 duplication in comparison with that of the control. The dots indicate individual markers in that region. Genomic gain is detected as an increase in the weighted log2 ratio and copy number state. The lower lines show the copy number in both cases (PNG 16.1 mb)


Graphical representation of cnLOH at the 3p21.31 region observed in 6 (17.6%) of the cases by ChAS software (Affymetrix, USA). Further, the software was set to a cutoff of ≥ 5 Mb for displaying loss of heterozygosity. The extent of cnLOH is represented using bold purple lines. For comparison, one control is represented showing absence of cnLOH (PNG 2.50 mb)

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Singh, V., Bala, R., Chakraborty, A. et al. Duplications in 19p13.3 are associated with male infertility. J Assist Reprod Genet 36, 2171–2179 (2019). https://doi.org/10.1007/s10815-019-01547-1

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  • Copy number variations
  • Genomic imbalances
  • Cytogenetic microarray
  • Infertility
  • Spermatogenesis