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 Weili Wang A1 Chaofeng Tu A1 Hongchuan Nie A1 Lanlan Meng A1 Yong Li A1 Shimin Yuan A1 Qianjun Zhang A1 Juan Du A1 Junpu Wang A1 Fei Gong A1 Liqing Fan A1 Guang-Xiu Lu A1 Ge Lin A1 Yue-Qiu Tan 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.