As a specific type of asthenoteratozoospermia,multiple morphological abnormalities of the sperm flagella(MMAF)is characterized by composite abnormalities,including absent,short,coiled,angulation,and irregular-caliber ...As a specific type of asthenoteratozoospermia,multiple morphological abnormalities of the sperm flagella(MMAF)is characterized by composite abnormalities,including absent,short,coiled,angulation,and irregular-caliber flagella.Mutations in cilia-and flagella-associated protein 43(CFAP43)are one of the main causative factors of MMAF established to date.To identify whether there are other CFAP43 mutations related to MMAF and to determine the clinical outcomes of assisted reproductive technology for patients with MMAF harboring different mutations,we recruited and screened 30 MMAF-affected Chinese men using a 22-gene next-generation sequencing panel.After systematic analysis,seven mutations in CFAP43,including five novel mutations and two previously reported mutations,were identified from four families and related to MMAF in an autosomal recessive pattern.Papanicolaou staining,immunofluorescence,and electronic microscopy further clarified the semen characteristics a nd abnormal sperm morphologies,including disorganized axonemal and peri-axonemal structures,of the CFAP43-deficient men.The female partners of two patients were pregnant after undergoing assisted reproductive technology through intracytoplasmic sperm injection,and one of them successfully gave birth to a healthy boy.This study significantly expands the mutant spectrum of CFAP43,and together with the available information regarding male infertility and MMAF,provides new information for the genetic diagnosis and counseling of MMAF in the future.展开更多
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...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。展开更多
基金the Natural Science Foundation of Chongqing(CSTC2021JCYJ-MSXMX0722)Chongqing Health Center for Women and Children(2020YJMS01).
文摘As a specific type of asthenoteratozoospermia,multiple morphological abnormalities of the sperm flagella(MMAF)is characterized by composite abnormalities,including absent,short,coiled,angulation,and irregular-caliber flagella.Mutations in cilia-and flagella-associated protein 43(CFAP43)are one of the main causative factors of MMAF established to date.To identify whether there are other CFAP43 mutations related to MMAF and to determine the clinical outcomes of assisted reproductive technology for patients with MMAF harboring different mutations,we recruited and screened 30 MMAF-affected Chinese men using a 22-gene next-generation sequencing panel.After systematic analysis,seven mutations in CFAP43,including five novel mutations and two previously reported mutations,were identified from four families and related to MMAF in an autosomal recessive pattern.Papanicolaou staining,immunofluorescence,and electronic microscopy further clarified the semen characteristics a nd abnormal sperm morphologies,including disorganized axonemal and peri-axonemal structures,of the CFAP43-deficient men.The female partners of two patients were pregnant after undergoing assisted reproductive technology through intracytoplasmic sperm injection,and one of them successfully gave birth to a healthy boy.This study significantly expands the mutant spectrum of CFAP43,and together with the available information regarding male infertility and MMAF,provides new information for the genetic diagnosis and counseling of MMAF in the future.
文摘目的探讨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。
