Novel DNAH17 mutations associated with fertilization failures after ICSI

Abstract

Objective

Fertilization is a key event in human reproduction. The male genetic factors associated with total fertilization failure (TFF) are largely unknown. To date, only mutations in PLCZ1 have been reported as male factors that result in human fertilization failure. Here, we report a novel DNAH17 mutation that resulted in male infertility and TFF.

Methods

A male patient with a three-year history of primary infertility presented with TFF after two failed cycles of intracytoplasmic sperm injection (ICSI). Use of donor sperm resulted in a healthy baby. Peripheral blood samples were taken from the proband and his parents and analyzed using whole exome and Sanger sequencing for clinical detection of genetic mutations.

Results

Compound heterozygous variants in DNAH17 were detected: NM_173628.4: c.1048 C > T and c.3390G > A; p.Arg350* and p.Met1130Ile. The latter variant was found to be highly conserved among mammals.

新的DNAH17突变与ICSI后受精失败相关 摘要

目的：受精是人类生殖的一个关键事件。与完全受精失败(TFF)相关的男性遗传因素在很大程度上是未知的。迄今为止, 只有PLCZ1突变被报道为导致人类受精失败的男性因素。在本文中, 我们报道了一个新的DNAH17突变, 该突变导致男性不育和完全受精失败。

方法：一名有三年原发性不孕病史的男性患者在两次卵胞浆内单精子注射失败后出现TFF。使用供体精子诞生了一个健康的婴儿。从先证者及其父母体内采集外周血样本, 并使用全外显子组和桑格测序分析来进行基因突变的临床检测。

结果：DNAH17中检测到复合杂合变异体：NM_173628.4: c.1048 C>T and c.3390G>A; p.Arg350* and p.Met1130IIe. 后者在哺乳类动物中高度保守。

Keywords:

• DNAH17
• fertilization failures

Disclosure statement

No potential conflict of interest was reported by the author(s).