Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3rd Qingchun East Road, Hangzhou, Zhejiang, China.
Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, Zhejiang, China.
Arch Gynecol Obstet. 2024 Oct;310(4):2211-2221. doi: 10.1007/s00404-024-07619-7. Epub 2024 Aug 12.
To explore the application possibility of macrocephalic sperm from a patient with 100% macrocephalic sperm and AURKC gene variations.
We diagnosed a case of macrozoospermia with 100% macrocephalic sperm and 39.5% multi-tailed spermatozoa by morphological analysis. Whole-exome sequencing (WES) was used for the patient and his wife. Sanger sequencing technique was used to verify the AURKC mutations in the patient's parents and his offspring. Sperm's ploidy was tested by flow cytometry. The couple asked for intra-couple ART therapy.
The patient presented novel compound heterozygous AURKC mutations (c.434C > T, c.497A > T) by WES. Sanger sequencing validation showed that variant of c.434C > T was observed in his father and c.497A > T was observed in his mother. Flow cytometry revealed that there existed a certain proportion of haploid sperm. Macrocephalic spermatozoa whose heads were smaller than the diameter of injection needle were selected for microinjection. A singleton pregnancy was achieved after embryo transfer. Prenatal diagnosis revealed that the fetus had normal chromosomal karyotype. Sanger sequencing technique showed that the fetus carried a c.434C > T mutation in one AURKC allele. A 3730 g healthy male fetus was delivered at term.
Our study reported a successful live birth from a patient with definite AURKC gene variants and may provide insights for such patients to choose donor sperm or their own sperm.
探索具有 100%大头精子和 AURKC 基因突变的患者大头精子的应用可能性。
我们通过形态学分析诊断了一例大头精子症患者，其大头精子比例为 100%，多尾精子比例为 39.5%。对患者及其妻子进行全外显子组测序（WES）。使用 Sanger 测序技术验证患者父母及其后代的 AURKC 突变。通过流式细胞术检测精子的倍性。夫妇要求进行夫妻间的 ART 治疗。
WES 显示患者存在新型复合杂合 AURKC 突变（c.434C>T，c.497A>T）。Sanger 测序验证显示，c.434C>T 变异在其父亲中存在，c.497A>T 变异在其母亲中存在。流式细胞术显示存在一定比例的单倍体精子。选择头小于注射针直径的大头精子进行微注射。胚胎移植后实现了单胎妊娠。产前诊断显示胎儿染色体核型正常。Sanger 测序技术显示胎儿携带一个 AURKC 等位基因的 c.434C>T 突变。足月分娩出一名 3730g 的健康男婴。
本研究报道了一例明确的 AURKC 基因突变患者成功活产，可为此类患者选择供精或自身精子提供参考。
