biostudies-literatureWang XPhD research startup foundation of the Third Affiliated Hospital of Zhengzhou UniversityResearch Grant from Wuhan Science and Technology BureauPostdoctoral Science Foundation Fund of ChinaNational Key Research and Development Program of China480https://www.ebi.ac.uk/biostudies/studies/S-EPMC9509617biostudies-literatureUnknown13(1)<h4>Background</h4>The most serious condition of male infertility is complete Sertoli cell-only syndrome (SCOS), which refers to the lack of all spermatogenic cells in the testes. The genetic cause of SCOS remains to be explored. We aimed to investigate the genetic cause of SCOS and assess the effects of the identified causative variant on human male germ cells.<h4>Methods</h4>Whole-exome sequencing was performed to identify potentially pathogenic variants in a man with complete SCOS, and Sanger sequencing was performed to verify the causative variant in this man and his father and brother. The pathogenic mechanisms of the causative variant were investigated by in vitro differentiation of human-induced pluripotent stem cells (hiPSCs) into germ cell-like cells.<h4>Results</h4>The homozygousStem cell research & therapyA homozygous PIWIL2 frameshift variant affects the formation and maintenance of human-induced pluripotent stem cell-derived spermatogonial stem cells and causes Sertoli cell-only syndrome.PMC9509617M2021M6911432017YFC10020002018060401011317Li HLi ZQu MXiong CWang XfalseA homozygous PIWIL2 frameshift variant affects the formation and maintenance of human-induced pluripotent stem cell-derived spermatogonial stem cells and causes Sertoli cell-only syndrome.<h4>Background</h4>The most serious condition of male infertility is complete Sertoli cell-only syndrome (SCOS), which refers to the lack of all spermatogenic cells in the testes. The genetic cause of SCOS remains to be explored. We aimed to investigate the genetic cause of SCOS and assess the effects of the identified causative variant on human male germ cells.<h4>Methods</h4>Whole-exome sequencing was performed to identify potentially pathogenic variants in a man with complete SCOS, and Sanger sequencing was performed to verify the causative variant in this man and his father and brother. The pathogenic mechanisms of the causative variant were investigated by in vitro differentiation of human-induced pluripotent stem cells (hiPSCs) into germ cell-like cells.<h4>Results</h4>The homozygous2022-01-01T00:00:00Z2022 Sep2026-06-01T02:26:07.795Z2025-04-04T14:21:20.139ZS-EPMC95096173615356710.1186/s13287-022-03175-6