Objective:This study aimed to screen for novel mutations in ACTL7A and expand the spectrum of known mutations responsible for recurrent fertilization failure.Methods:Whole-exome sequencing was performed on samples fro...Objective:This study aimed to screen for novel mutations in ACTL7A and expand the spectrum of known mutations responsible for recurrent fertilization failure.Methods:Whole-exome sequencing was performed on samples from couples who experienced recurrent assisted reproductive technology failure and visited the General Hospital of Ningxia Medical University.Western blotting and quantitative Real-time PCR were used to investigate the effects of the mutation on HEK293T cells.Results:Samples from 12 couples with total fertilization failure or poor fertilization(fertilization rate<20%)were subjected to whole-exome sequencing,and a novel homozygous protein-truncating mutation(c.1101dupC,p.S368Qfs*5)in ACTL7A was identified in a patient with recurrent poor fertilization.The mutant resulted in a truncated protein as well as decreased protein expression level in HEK293T cells.Conclusions:Our findings expand the mutational and phenotypic spectrum of ACTL7A,thus providing a potential diagnostic marker for fertilization failure due to male factors.展开更多
基金Foundation of Science and Technology Commission of Shanghai Municipality(17JC1400902)Merck Serono China Research Fund for Fertility Experts(MerckSerono CREATE20150170)
文摘Objective:This study aimed to screen for novel mutations in ACTL7A and expand the spectrum of known mutations responsible for recurrent fertilization failure.Methods:Whole-exome sequencing was performed on samples from couples who experienced recurrent assisted reproductive technology failure and visited the General Hospital of Ningxia Medical University.Western blotting and quantitative Real-time PCR were used to investigate the effects of the mutation on HEK293T cells.Results:Samples from 12 couples with total fertilization failure or poor fertilization(fertilization rate<20%)were subjected to whole-exome sequencing,and a novel homozygous protein-truncating mutation(c.1101dupC,p.S368Qfs*5)in ACTL7A was identified in a patient with recurrent poor fertilization.The mutant resulted in a truncated protein as well as decreased protein expression level in HEK293T cells.Conclusions:Our findings expand the mutational and phenotypic spectrum of ACTL7A,thus providing a potential diagnostic marker for fertilization failure due to male factors.
