CFAP43或CFAP44基因突变致精子鞭毛多发形态异常患者的辅助生殖助孕结局研究

Assisted reproduction outcomes for patients with multiple morphological abnormalities of the sperm flagella caused by CFAP43 or CFAP44 gene mutations

目的探讨CFAP43或CFAP44基因突变致精子鞭毛多发形态异常(multiple morphological abnormalities of the flagella,MMAF)患者行卵胞质内单精子注射(intracytoplasmic sperm injection,ICSI)助孕的临床结局。方法回顾性队列研究分析2014年9月至2020年7月期间于安徽医科大学第一附属医院妇产科生殖医学中心就诊的121例MMAF男性不育症患者的临床资料和基因检测结果,纳入9例CFAP43或CFAP44基因突变MMAF患者,5例MMAF患者(P3、P5、P7、P8和P9)选择ICSI助孕治疗,统计并分析这5例患者ICSI助孕的临床结局。结果Sanger测序证实9例MMAF患者携带CFAP43或CFAP44基因双等位基因突变,其中3例患者的突变位点以往未曾报道,分别为CFAP43基因的新发纯合突变(c.4132delC:p.Arg1378Glufs*10)和新发复合杂合突变(c.3938G>A:p.Arg1313Gln;c.4342G>A:p.Glu1448Lys)以及CFAP44基因的新发复合杂合突变(c.1718C>A:p.Pro573His;c.4075G>A:p.Glu1359Lys)。5例MMAF患者夫妇接受5个ICSI周期,已生育4个健康亲生子代。CFAP43或CFAP44基因突变MMAF患者组ICSI受精率为76.47%(39/51),5例患者中临床妊娠3例,活产3例。与DNAH1基因突变MMAF患者组和严重少弱精子症患者组相比,CFAP43或CFAP44基因突变MMAF患者ICSI助孕结局差异均无统计学意义(均P>0.05)。结论CFAP43或CFAP44基因突变会导致精子严重的鞭毛畸形和运动能力下降,是MMAF的重要病因。ICSI技术可以有效地解决CFAP43或CFAP44基因突变MMAF患者的生育难题。

Objective To investigate the clinical outcomes of patients with multiple morphological abnormalities of the flagella(MMAF)caused by CFAP43 or CFAP44 gene mutations following intracytoplasmic sperm injection(ICSI).Methods Clinical data and genetic information were retrospectively analyzed for 121 MMAF patients who attended Reproductive Medicine Center,Department of Obstetrics and Gynecology,the First Affiliated Hospital of Anhui Medical University during September 2014 to July 2020.Totally 9 MMAF patients were identified to carry CFAP43 or CFAP44 mutations,5 of them(P3,P5,P7,P8,and P9)received ICSI treatments,the ICSI outcomes were further analyzed.Results Sanger sequencing validated 9 MMAF patients harboring CFAP43 or CFAP44 biallelic mutations,our study firstly identified a novel homozygous mutation of CFAP43(c.4132delC:p.Arg1378Glufs*10),novel compound heterozygous mutations of CFAP43(c.3938G>A:p.Arg1313Gln;c.4342G>A:p.Glu1448Lys)and novel compound heterozygous mutations of CFAP44(c.1718C>A:p.Pro573His;c.4075G>A:p.Glu1359Lys).The 5 MMAF patients underwent 5 ICSI cycles,4 healthy offspring were obtained.The rate of fertilization of CFAP43-or CFAP44-mutated MMAF patients following ICSI was 76.47%(39/51),3 patients'wife got clinical pregnancy,3 patients got live birth delivery,respectively.No significant differences were found in ICSI outcomes among CFAP43-mutated or CFAP44-mutated MMAF patients,DNAH1-mutated MMAF patients,and severe oligoasthenozoospermia group(all P>0.05).Conclusion CFAP43 or CFAP44 mutations are responsible for the malformation of sperm flagella and decrease of sperm motility,and validated as the important genetic causes of MMAF.CFAP43-or CFAP44-mutated MMAF patients could have a favorable treatment outcome following ICSI.