The American Journal of Human GeneticsGeneticsPeer-reviewed journal article
SYCP2 translocation-mediated dysregulation and frameshift variants cause human male infertility
Samantha L.P. SchilitiD, Shreya MenoniD, Corinna FriedrichiD, Tammy Kammin, Ellen WilchiD, Carrie Hanscom, Sizun JiangiD, Sabine KlieschiD, Michael E. TalkowskiiD, Frank TüttelmanniD, Amy J. MacQueeniD, Cynthia Casson MortoniD
Abstract
Infertility is one of the most common disorders for men of reproductive age. To identify novel genetic etiologies, we studied a male with severe oligozoospermia and 46, XY,t(20;22)(q13.3;q11.2). We identified exclusive overexpression of SYCP2 from the der(20) allele that is hypothesized to result from enhancer adoption. Modeling the dysregulation in budding yeast resulted in disruption of the synaptonemal complex, a common cause of defective spermatogenesis in mammals. Exome sequencing of infertile males revealed three novel heterozygous SYCP2 frameshift variants in additional subjects with cryptozoospermia and azoospermia. This study provides the first evidence of SYCP2-mediated male infertility in humans.
- organism: human
- assay: whole-exome sequencing
- research focus: variant calling
- approach: statistical model
- Citations
- 95
- FWCI
- 14.10
- Field percentile
- top 1%
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