Reproductive Medicine Center, Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, 154, Anshan Road, Heping District, Tianjin, 300052, China.
BMC Womens Health. 2020 Nov 4;20(1):246. doi: 10.1186/s12905-020-01111-5.
Fertilization failure after intracytoplasmic sperm injection continues to affect couples and the etiology is not well-understood.
We characterized a couple with 2-year history of primary unexplained infertility. Three different assisted reproduction attempts (IVF + rescue ICSI, ICSI and ICSI-AOA) showed repeated fertilization failure for MII oocyte retrieval after controlled ovarian hyperstimulation. After whole-exome sequencing and sanger sequencing of the couple and their family members, variant pathogenicity was assessed using SIFT, PolyPhen2, Mutation Taster, and Human Splicing Finder software. We identified novel compound heterozygous mutations, c.1535 + 3A > G and c.946C > T (p. Leu316Phe), in WEE2 in the female proband. Trios analysis of the variations revealed an autosomal recessive pattern. c.1535 + 3A > G in WEE2 was predicted to break the wild-type donor site and affect splicing, and the missense mutation c.946C > T (p. Leu316Phe) of WEE2 was predicted to be pathogenic.
A novel compound heterozygous mutation in WEE2 was identified in an infertile female who experienced repeated fertilization failure even after ICSI-AOA. These novel mutations in WEE2 provided genetic evidence for fertilization failure.
卵胞浆内单精子注射受精失败仍困扰着夫妇，其病因尚未完全阐明。
我们对一对有 2 年原发性不明原因不孕史的夫妇进行了研究。在控制性卵巢超刺激后，对 MII 卵母细胞进行取卵时，这对夫妇经历了 3 次不同的辅助生殖尝试（IVF+rescue ICSI、ICSI 和 ICSI-AOA），均显示出反复受精失败。对夫妇及其家庭成员进行全外显子组测序和 Sanger 测序后，使用 SIFT、PolyPhen2、Mutation Taster 和 Human Splicing Finder 软件评估变异的致病性。我们在女性先证者中发现了 WEE2 的新型复合杂合突变 c.1535+3A>G 和 c.946C>T(p.Leu316Phe)。对变异的三代分析显示出常染色体隐性遗传模式。WEE2 中的 c.1535+3A>G 被预测会破坏野生型供体位点并影响剪接，而 WEE2 的错义突变 c.946C>T(p.Leu316Phe)被预测为致病性的。
在一名反复受精失败的不孕女性中发现了 WEE2 的一种新型复合杂合突变，即使在 ICSI-AOA 后也经历了反复受精失败。WEE2 中的这些新突变为受精失败提供了遗传证据。
