RT Journal Article SR Electronic T1 Mutations in ZP4 are associated with abnormal zona pellucida and female infertility JF Journal of Clinical Pathology JO J Clin Pathol FD BMJ Publishing Group Ltd and Association of Clinical Pathologists SP 201 OP 204 DO 10.1136/jclinpath-2020-207170 VO 75 IS 3 A1 Xiaoli Wei A1 Youzhu Li A1 Qicai Liu A1 Wensheng Liu A1 Xiaohong Yan A1 Xingshen Zhu A1 Dekun Zhou A1 Yingpu Tian A1 Fuxing Zhang A1 Na Li A1 Zhongxian Lu YR 2022 UL http://jcp.bmj.com/content/75/3/201.abstract AB Background The zona pellucida (ZP) of human oocytes plays essential protective roles in sperm–egg interactions during fertilisation and embryo development. ZP4-null female rabbits exhibit a thin and irregular ZP, which severely impairs embryo development and fertility. However, the effects of ZP4 defect on human female reproduction remain unknown.Methods and results We performed whole-exome sequencing in 26 female patients with abnormal (thin and irregular) ZP and identified heterozygous variants in ZP4 (OMIM: 613514) from 3 patients (approximately 11%). No ZP4 variant was found in the 30 control women with proven fertility. We constructed ZP4-mutated plasmids and found that the variants reduced the secretion of ZP4 in vitro. Lower suction pressure facilitated egg retrieval, and intracytoplasmic sperm injection (ICSI) was a desirable treatment for ZP4-mutated patients with abnormal ZP.Conclusions We identified ZP4 as a novel gene for human abnormal ZP and found that lower suction pressure and ICSI are efficient treatment strategies.