RT Journal Article SR Electronic T1 Mutation in TDRD9 causes non-obstructive azoospermia in infertile men JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 633 OP 639 DO 10.1136/jmedgenet-2017-104514 VO 54 IS 9 A1 Maram Arafat A1 Iris Har-Vardi A1 Avi Harlev A1 Eliahu Levitas A1 Atif Zeadna A1 Maram Abofoul-Azab A1 Victor Dyomin A1 Val C Sheffield A1 Eitan Lunenfeld A1 Mahmoud Huleihel A1 Ruti Parvari YR 2017 UL http://jmg.bmj.com/content/54/9/633.abstract AB Background Azoospermia is diagnosed when sperm cells are completely absent in the ejaculate even after centrifugation. It is identified in approximately 1% of all men and in 10%–20% of infertile males. Non-obstructive azoospermia (NOA) is characterised by the absence of sperm due to either a Sertoli cell-only pattern, maturation arrest, hypospermatogenesis or mixed patterns. NOA is a severe form of male infertility, with limited treatment options and low fertility success rates. In the majority of patients, the cause for NOA is not known and mutations in only a few genes were shown to be causative.Aim We investigated the cause of maturation arrest in five azoospermic infertile men of a large consanguineous Bedouin family.Methods and results Using whole genome genotyping and exome sequencing we identified a 4 bp deletion frameshift mutation in TDRD9 as the causative mutation with a Lod Score of 3.42. We demonstrate that the mutation results in a frameshift as well as exon skipping. Immunofluorescent staining with anti-TDRD9 antibody directed towards the N terminus demonstrated the presence of the protein in testicular biopsies of patients with an intracellular distribution comparable to a control biopsy. The mutation does not cause female infertility.Conclusion This is the first report of a recessive deleterious mutation in TDRD9 in humans. The clinical phenotype recapitulates that observed in the Tdrd9 knockout mice where this gene was demonstrated to participate in long interspersed element-1 retrotransposon silencing. If this function is preserved in human, our data underscore the importance of maintaining DNA stability in the human male germ line.