3例SUN5基因变异导致无头精子症的遗传学分析和助孕治疗结局

Genetic analysis of three cases of acephalic spermatozoa syndrome caused by SUN5 mutation and the outcome of assisted reproductive technology

畸形精子症是男性不育的常见原因之一[1],其中无头精子症(acephalic spermatozoa syndrome,ASS)是一种严重导致男性不育的罕见畸形精子症,其特征是精液中含有无头精子尾部和一些松散的精子头部,主要表现为头颈部连接处异常[2-3],精子在电子显微镜下通常显示精子头部和尾部之间缺少植入窝和基板[4]。ASS有2种亚型:一种类型表现为没有细胞核的小“针头样”精子,另一种类型是头颈部错误连接的精子[3,5]。

To explore the genetic causes of 3 male infertility patients with acephalospermia and the outcome of assisted reproductive technology.Clinical diagnosis,sperm morphology examination,sperm transmission electron microscopy examination were performed on 3 patients,and the whole exome sequencing technology was used for screening,Sanger sequencing verification,mutation pathogenicity analysis,and protein sequence homology comparison.Assisted reproductive technology was implemented to assist pregnancy treatment.The 3 patients were all sporadic infertile men,aged 25,42 and 26 years,and there was no obvious abnormality in the general physical examination.Male external genitalia developed normally,bilateral testicles were normal in volume,and bilateral epididymis and spermatic vein were palpated without nodules,cysts,and tenderness.Repeated semen analysis showed that a large number of immature sperm could be seen,and they had the ability to move.The SUN5 gene of the 3 male infertile patients was a case of homozygous missense mutation c.7C>T(p.Arg3Trp),a case of compound heterozygous missense mutation c.1067G>A(p.Arg356His)and nonsense mutation c.216G>A(p.Trp72*)and a case of homozygous missense mutation c.1043A>T(p.Asn348Ile),of which c.7C>T(p.Arg3Trp)and c.1067G>A(p.Arg356His)were new variants that had not been reported.SIFT,Mutation Taster and PolyPhen-2 software function prediction results were all harmful,the nonsense mutation c.216G>A(p.Trp72*)led to the premature termination of peptide chain synthesis which might have a greater impact on protein function.The homology regions in the protein sequence homology alignment were all highly conserved.The 3 male patients and their spouses obtained 4 biological offspring through intracytoplasmic sperm injection,all of which were boys,and one of them was a twin.Three male infertile patients might be caused by SUN5 gene mutations.Such patients could obtain their biological offspring through assisted reproductive technology.It was still necessary to pay attention to the genetic risk of ASS,it was recommended that both men and women conduct genetic counseling and screening at the same time.In clinical diagnosis,whole exome sequencing technology could be used to perform auxiliary examinations to determine the treatment plan and assisted reproductive methods as soon as possible to reduce the burden on the family and society.The newly discovered mutation sites of SUN5 gene provided clues and directions for elucidating the pathogenic mechanism,and at the same time expanded the pathogenic mutation spectrum of ASS.