RT Journal Article SR Electronic T1 Biallelic mutations in CFAP65 lead to severe asthenoteratospermia due to acrosome hypoplasia and flagellum malformations JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 750 OP 757 DO 10.1136/jmedgenet-2019-106031 VO 56 IS 11 A1 Wang, Weili A1 Tu, Chaofeng A1 Nie, Hongchuan A1 Meng, Lanlan A1 Li, Yong A1 Yuan, Shimin A1 Zhang, Qianjun A1 Du, Juan A1 Wang, Junpu A1 Gong, Fei A1 Fan, Liqing A1 Lu, Guang-Xiu A1 Lin, Ge A1 Tan, Yue-Qiu YR 2019 UL http://jmg.bmj.com/content/56/11/750.abstract AB Background The genetic causes for most male infertility due to severe asthenozoospermia remain unclear.Objective Our objective was to identify unknown genetic factors in 47 patients with severe asthenozoospermia from 45 unrelated Chinese families.Methods We performed whole exome sequencing of 47 individuals with severe asthenozoospermia from 45 unrelated families. Mutation screening was performed in a control cohort of 637 individuals, including 219 with oligoasthenospermia, 195 with non-obstructive azoospermia and 223 fertile controls. Ultrastructural and immunostaining analyses of patients’ spermatozoa were performed to characterise the effect of variants.Results One homozygous non-sense mutation (NM_194302, c.G5341T:p.E1781X), two compound heterozygous mutations (c.C2284T:p.R762X and c.1751delC:p.P584fs) and two compound heterozygous mutations (c.5714_5721del:p.L1905fs and c.C3021A:p.N1007K) were identified in CFAP65 of three individuals with completely immotile spermatozoa, respectively. No biallelic deleterious variants of CFAP65 were detected in the control cohort of 637 individuals. Ultrastructural and immunostaining analyses of spermatozoa from two patients showed highly aberrant sperm morphology with severe defects such as acrosome hypoplasia, disruption of the mitochondrial sheath and absence of the central pair complex.Conclusion To the best of our knowledge, we are the first to report that CFAP65 mutations may cause spermatozoa to be completely immotile.