Globozoospermia has been reported to be a rare but severe causation of male infertility,which results from the failure of acrosome biogenesis and sperm head shaping.Variants of dpy-19-like 2(DPY19L2)are highly related...Globozoospermia has been reported to be a rare but severe causation of male infertility,which results from the failure of acrosome biogenesis and sperm head shaping.Variants of dpy-19-like 2(DPY19L2)are highly related to globozoospermia,but related investigations have been mainly performed in patients from Western countries.Here,we performed a screening of DPY19L2 variants in a cohort of Chinese globozoospermic patients and found that five of nine patients carried DPY19L2 deletions and the other four patients contained novel DPY19L2 point mutations,as revealed by whole-exome sequencing.Patient 3(P3)contained a heterozygous variant(c.2126+5G>A),P6 contained a homozygous nonsense mutation(c.1720C>T,p.Arg574*),P8 contained compound heterozygous variants(c.H82-1184delATCf p.Leu394_Ser395deIinsPhe;c.368A>T,p.Hisl23Arg),and P9 contained a heterozygous variant(c.H82-1184delATCTTI frameshift).We also reported intracytoplasmic sperm injection(ICSI)outcomes in the related patients,finding that ICSI followed by assisted oocyte activation(AOA)with calcium ionophore achieved high rates of live births.In summary,the infertility of these patients results from DPY19L2 dysfunction and can be treated by ICSI together with AOA.展开更多
Klinefelter syndrome and Y-chromosomal microdeletion analyses were once the only two genetic tests offered to infertile men. Analyses of aurora kinase C （AURKCj and DPY19L2 are now recommended for patients presenting...Klinefelter syndrome and Y-chromosomal microdeletion analyses were once the only two genetic tests offered to infertile men. Analyses of aurora kinase C （AURKCj and DPY19L2 are now recommended for patients presenting macrozoospermia and globozoospermia, respectively, two rare forms of teratozoospermia particularly frequent among North African men. We carried out genetic analyses on Algerian patients, to evaluate the prevalence of these syndromes in this population and to compare it with the expected frequency of Klinefelter syndrome and Y-microdeletions. We carried out a retrospective study on 599 consecutive patients consulting for couple infertility at the assisted reproduction unit of the Ibn Rochd Clinique, Constantine, Algeria. Abnormal sperm parameters were observed in 404 men. Fourteen and seven men had typical macrozoospermia and globozoospermia profiles, respectively. Molecular diagnosis was carried out for these patients, for the AURKC and DPY19L2 genes. Eleven men with macrozoospermia had a homozygous AURKC mutation （79%）, corresponding to 2.7% of all patients with abnormal spermograms. All the men with globozoospermia studied （n = 5）, corresponding to 1.2% of all infertile men, presented a homozygous DPY19L2deletion. By comparison, we would expect 1.6% of the patients in this cohort to have Klinefelter syndrome and 0.23% to have Y-microdeletion. Our findings thus indicate that AURKCmutations are more frequent than Klinefelter syndrome and constitute the leading genetic cause of infertility in North African men. Furthermore, we estimate that AURKCand DPY19L2 molecular defects are 10 and 5 times more frequent, respectively, than Y-microdeletions.展开更多
文摘Globozoospermia has been reported to be a rare but severe causation of male infertility,which results from the failure of acrosome biogenesis and sperm head shaping.Variants of dpy-19-like 2(DPY19L2)are highly related to globozoospermia,but related investigations have been mainly performed in patients from Western countries.Here,we performed a screening of DPY19L2 variants in a cohort of Chinese globozoospermic patients and found that five of nine patients carried DPY19L2 deletions and the other four patients contained novel DPY19L2 point mutations,as revealed by whole-exome sequencing.Patient 3(P3)contained a heterozygous variant(c.2126+5G>A),P6 contained a homozygous nonsense mutation(c.1720C>T,p.Arg574*),P8 contained compound heterozygous variants(c.H82-1184delATCf p.Leu394_Ser395deIinsPhe;c.368A>T,p.Hisl23Arg),and P9 contained a heterozygous variant(c.H82-1184delATCTTI frameshift).We also reported intracytoplasmic sperm injection(ICSI)outcomes in the related patients,finding that ICSI followed by assisted oocyte activation(AOA)with calcium ionophore achieved high rates of live births.In summary,the infertility of these patients results from DPY19L2 dysfunction and can be treated by ICSI together with AOA.
文摘Klinefelter syndrome and Y-chromosomal microdeletion analyses were once the only two genetic tests offered to infertile men. Analyses of aurora kinase C （AURKCj and DPY19L2 are now recommended for patients presenting macrozoospermia and globozoospermia, respectively, two rare forms of teratozoospermia particularly frequent among North African men. We carried out genetic analyses on Algerian patients, to evaluate the prevalence of these syndromes in this population and to compare it with the expected frequency of Klinefelter syndrome and Y-microdeletions. We carried out a retrospective study on 599 consecutive patients consulting for couple infertility at the assisted reproduction unit of the Ibn Rochd Clinique, Constantine, Algeria. Abnormal sperm parameters were observed in 404 men. Fourteen and seven men had typical macrozoospermia and globozoospermia profiles, respectively. Molecular diagnosis was carried out for these patients, for the AURKC and DPY19L2 genes. Eleven men with macrozoospermia had a homozygous AURKC mutation （79%）, corresponding to 2.7% of all patients with abnormal spermograms. All the men with globozoospermia studied （n = 5）, corresponding to 1.2% of all infertile men, presented a homozygous DPY19L2deletion. By comparison, we would expect 1.6% of the patients in this cohort to have Klinefelter syndrome and 0.23% to have Y-microdeletion. Our findings thus indicate that AURKCmutations are more frequent than Klinefelter syndrome and constitute the leading genetic cause of infertility in North African men. Furthermore, we estimate that AURKCand DPY19L2 molecular defects are 10 and 5 times more frequent, respectively, than Y-microdeletions.
