Compound heterozygous mutations in PMFBP1 cause acephalic spermatozoa syndrome:A case report

BACKGROUND Acephalic spermatozoa syndrome(ASS)is an extremely rare form of severe teratozoospermia,where in most of the sperm either appear to lack heads or have disconnected or poorly connected heads and tails.CASE SUMMARY We reported the case of a male patient with secondary infertility whose sperm showed typical ASS upon morphological analysis.Whole-exome sequencing was performed on the patient’s peripheral blood,which revealed two heterozygous variants of the PMFBP1 gene:PMFBP1c.414+1G>T(p.?)and PMFBP1c.393del(p.C132Afs*3).CONCLUSION It is speculated that the compound homozygous mutation of PMFBP1 may be the cause of ASS.We conducted a literature review in order to provide the basis for genetic counseling and clinical diagnosis of patients with ASS.

Biallelic mutations in spermatogenesis and centriole-associated 1 like(SPATC1L)cause acephalic spermatozoa syndrome and male infertility

Acephalic spermatozoa syndrome is a rare type of teratozoospermia that severely impairs the reproductive ability of male patients,and genetic defects have been recognized as the main cause of acephalic spermatozoa syndrome.Spermatogenesis and centrioleassociated 1 like(SPATC1L)is indispensable for maintaining the integrity of sperm head-to-tail connections in mice,but its roles in human sperm and early embryonic development remain largely unknown.Herein,we conducted whole-exome sequencing(WES)of 22 infertile men with acephalic spermatozoa syndrome.An in silico analysis of the candidate variants was conducted,and WES data analysis was performed using another cohort consisting of 34 patients with acephalic spermatozoa syndrome and 25 control subjects with proven fertility.We identified biallelic mutations in SPATC1L(c.910C>T:p.Arg304Cys and c.994G>T:p.Glu332X)from a patient whose sperm displayed complete acephalia.Both SPATC1L variants are rare and deleterious.SPATC1L is mainly expressed at the head–tail junction of elongating spermatids.Plasmids containing pathogenic variants decreased the level of SPATC1L in vitro.Moreover,none of the patient’s four attempts at intracytoplasmic sperm injection(ICSI)resulted in a transplantable embryo,which suggests that SPATC1L defects might affect early embryonic development.In conclusion,this study provides the first identification of SPATC1L as a novel gene for human acephalic spermatozoa syndrome.Furthermore,WES might be applied for patients with acephalic spermatozoa syndrome who exhibit reiterative ICSI failures.

Genetic pathogenesis of acephalic spermatozoa syndrome:past,present,and future

Acephalic spermatozoa syndrome(ASS)is one of the most severe spermatogenic failures of all infertility in men.The cognition of ASS has experienced a tortuous process.Over the past years,with the in-depth understanding of spermatogenesis and the emergence of new genetic research technologies,the unraveling of the genetic causes of spermatogenic failure has become highly active.From these advances,we established a genetic background and made significant progress in the discovery of the genetic causes of ASS.It is important to identify pathogenic genes and mutations in ASS to determine the biological reasons for the occurrence of the disease as well as provide genetic diagnosis and treatment strategies for patients with this syndrome.In this review,we enumerate various technological developments,which have made a positive contribution to the discovery of candidate genes for ASS from the past to the present.Simultaneously,we summarize the known genetic etiology of this phenotype and the clinical outcomes of treatments in the present.Furthermore,we propose perspectives for further study and application of genetic diagnosis and assisted reproductive treatment in the future.